EP0850229A1 - Pyrimidin-4-one derivatives, their use as herbicides, intermediates for their production and processes for producing these compounds - Google Patents

Pyrimidin-4-one derivatives, their use as herbicides, intermediates for their production and processes for producing these compounds

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Publication number
EP0850229A1
EP0850229A1 EP96925969A EP96925969A EP0850229A1 EP 0850229 A1 EP0850229 A1 EP 0850229A1 EP 96925969 A EP96925969 A EP 96925969A EP 96925969 A EP96925969 A EP 96925969A EP 0850229 A1 EP0850229 A1 EP 0850229A1
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EP
European Patent Office
Prior art keywords
alkyl
compound
compound according
carbonyl
hydrogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP96925969A
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German (de)
French (fr)
Inventor
Masayuki Enomoto
Hisayuki Hoshi
Yuzuru Sanemitsu
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Sumitomo Chemical Co Ltd
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Sumitomo Chemical Co Ltd
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Publication date
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Publication of EP0850229A1 publication Critical patent/EP0850229A1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to pyrimidin-4-one derivatives, their use, inter ⁇ mediates for their production, and processes for producing these intermediates.
  • the present inventors have intensively studied to find a compound having excellent herbicidal activity. As a result, they have found that pyrimidin-4-one deriva ⁇ tives represented by formula [ 1 ] as depicted below have excellent herbicidal activity, thereby completing the present invention.
  • R 1 is hydrogen or C 1 -C3 alkyl
  • R 2 is C1-C3 alkyl optionally substituted with one or more halogen atoms
  • R 3 is alkyl optionally substituted with one or more halogen atoms, C3-C6 alkenyl, or C3-C6 alkynyl
  • Q is substituted phenyl (herein ⁇ after referred to as the present compound(s)); and a herbicide containing it as an active ingredient.
  • the present invention also provides a process for producing compound [ 1 ], which comprises reacting a compound of the formula:
  • D is chlorine, bromine, iodine, methanesulfonyloxy, trifluoromethanesulfonyl- oxy, or p-toluenesulfonyloxy; and R 3 is as defined above.
  • the present invention further provides a compound of the formula:
  • R 21 is C--C3 alkyl substituted with one or more halogen atoms, which is useful as an intermediate for the production of some of the present compounds; and a process for producing a compound of the formula:
  • R 19 and R 20 are independently -C3 alkyl, and Q and R 1 are as defined above, with a compound of the formula:
  • Examples of Q in the present invention include [Q-l], [Q-2], [Q-3], [Q-4], or [Q-5] of the formula:
  • X is hydrogen or halogen
  • Y is halogen, nitro, cyano, or trifluoromethyl
  • Z 1 is oxygen, sulfur, NH, or methylene
  • Z 2 is oxygen or sulfur; n is 0 or 1 ;
  • R 4 is hydrogen or C1-C3 alkyl
  • R 5 is hydrogen, C 1-C6 alkyl, C- -C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, cyano alkyl, C2-C8 alkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, carboxy C 1 -C6 alkyl, (Ci-C ⁇ alkoxy)carbonyl C 1 -C6 alkyl, ⁇ (C 1 -C4 alkoxy) C 1 -C4 alkoxy ⁇ carbonyl Cj-C ⁇ alkyl, (C3-C8 cycloalkoxy)carbonyl- C ⁇ -C 6 alkyl, -CH 2 CON(R u )R 12 , -CH 2 COON(R n )R 12 , -CH(C ⁇ -C 4 alkyl)CON- (R
  • R 6 is C 1-C6 alkyl, C ⁇ -C(, haloalkyl, formyl, cyano, carboxyl, hydroxy C ⁇ -C 6 alkyl, C] -C 6 alkoxy C ⁇ -C 6 alkyl, C ⁇ -C 6 alkoxy C ⁇ -C 6 alkoxy C--C 6 alkyl, (C ]-C6 alkyl)carbonyloxy Cj-C ⁇ alkyl, (Cj-C ⁇ haloalkyl)carbonyloxy Cj-C ⁇ alkyl, (C]-C6 alkoxy)carbonyl, or (C ⁇ -C(, alkyl)carbonyl;
  • R 7 is hydrogen or Ci -C alkyl
  • R 8 is C ⁇ -C 6 alkyl, C ⁇ -C 6 haloalkyl, C ⁇ -C 6 hydroxyalkyl, C -C 8 alkoxy ⁇ alkyl, C3-C10 alkoxyalkoxyalkyl, (C1-C5 alkyl)carbonyloxy Cj-C ⁇ alkyl, (Cj-C ⁇ halo- alkyl)carbonyloxy Cj-C6 alkyl, carboxyl, carboxy C- -C6 alkyl, (Cj-Cs alkoxy)- carbonyl, (C--C6 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C8 alkenyl- oxy)carbonyl, (C3-C8 alkynyloxy)carbonyl, aminocarbonyl, ( -C6 alkyl)amino- carbonyl, di(C]-C6 alkyl)aminocarbonyl,
  • Examples of the -C3 alkyl represented by R 1 include methyl, ethyl, and isopropyl.
  • Examples of the C 1 -C3 alkyl optionally substituted with one or more halogen atoms, which is represented by R 2 include methyl, ethyl, isopropyl, trichloromethyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.
  • Examples of the C--C6 alkyl optionally substituted with one or more halogen atoms, which is represented by R 3 , include methyl, ethyl, isopropyl, difluoromethyl, and bromodifluoromethyl.
  • Examples of the C3-C6 alkenyl represented by R 3 include allyl and 1-methyl- 2-propenyl.
  • Examples of the C3-C6 alkynyl represented by R 3 include propargyl and 1 -methyl-2-propynyl.
  • Examples of the halogen represented by X, Y, and B include chlorine, fluorine, bromine, and iodine.
  • Examples of the Cj -C6 alkyl represented by R 10 include methyl, ethyl, isopropyl, propyl, isobutyl, butyl, t-butyl, amyl, isoamyl, and t-amyl.
  • Examples of the Cj-C ⁇ haloalkyl represented by R 10 include difluoromethyl, tetrafluoroethyl, and 2,2,2-trifluoroethyl.
  • Examples of the C3-C8 cycloalkyl represented by R 10 include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • Examples of the C3-C6 alkenyl represented by R 10 include allyl, l-methyl-2- propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl.
  • Examples of the C3-C6 haloalkenyl represented by R 10 include 2-chloro-2- propenyl and 3,3-dichloro-2-propenyl.
  • Examples of the C3-C6 alkynyl represented by R 10 include propargyl, 1 -methyl-2-propynyl, 2-butynyl, and l,l-dimethyl-2-propynyl.
  • Examples of the C3-C6 haloalkynyl represented by R 10 include 3-bromo-2- propynyl.
  • Examples of the cyano -C6 alkyl represented by R 10 include cyanomethyl.
  • Examples of the C2-C8 alkoxyalkyl represented by R 10 include methoxy- methyl, methoxyethyl, ethoxymethyl, and ethoxyethyl.
  • Examples of the C2-C8 alkylthioalkyl represented by R 10 include methylthio- methyl.
  • Examples of the carboxy C--C6 alkyl represented by R 10 include carboxy- methyl, 1 -carboxyethyl, and 2-carboxyethyl.
  • Examples of the (C ⁇ -C(, alkoxy)carbonyl -C6 alkyl represented by R 10 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopro- poxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycar- bonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonyl- ethyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1-iso- propoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxy- carbonylethyl, 1 -amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-amyloxy
  • Examples of the (Ci-C ⁇ haloalkoxy)carbonyl Cj-C6 alkyl represented by R 10 include 2,2,2-trifluoroethoxycarbonylmethyl.
  • Examples of the ⁇ (C1 -C4 alkoxy) C 1 -C4 alkoxy ⁇ carbonyl Cj-C ⁇ alkyl represented by R 10 include methoxymethoxycarbonylmethyl and 1-methoxymethoxy- carbonylethyl.
  • Examples of the (C3-C8 cycloalkoxy)carbonyl C 1 -C6 alkyl represented by R ⁇ ° include cyclobutyloxycarbonylmethyl, cyclopentyloxycarbonylmethyl, cyclohexyl- oxycarbonylmethyl, 1 -cyclobutyloxycarbonylethyl, 1-cyclopentyloxycarbonylethyl, and 1 -cyclohexyloxycarbonylethyl.
  • Examples of the C 1 -C6 alkyl represented by R 1 1 and R 12 include methyl, ethyl, propyl, butyl, isopropyl, and isobutyl.
  • Examples of the C--C6 haloalkyl represented by R 1 1 and R 12 include chloro- ethyl and bromoethyl.
  • Examples of the C3-C6 alkenyl represented by R 1 1 and R 12 include allyl, l-methyl-2-propenyl, and 3-butenyl.
  • Examples of the C3-C6 alkynyl represented by R 1 1 and R 12 include propargyl and l-methyl-2-propynyl.
  • Examples of the cyano Ci-C ⁇ alkyl represented by R 1 1 and R 12 include cyanomethyl.
  • Examples of the C 2 -C8 alkoxyalkyl represented by R 1 1 and R 12 include methoxymethyl and ethoxyethyl.
  • Examples of the C 2 -Cg alkylthioalkyl represented by R 1 1 and R 12 include methylthiomethyl and methylthioethyl.
  • Examples of the carboxy C- -C6 alkyl represented by R 1 1 and R 12 include carboxymethyl and 1-carboxyethyl.
  • Examples of the ( -C6 alkoxy)carbonyl C--C6 alkyl represented by R 1 1 and R • 2 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxy- carbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycar- bonylmethyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1 -isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobut ⁇ xycarbonylethyl, 1-t- butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1 -isoamyloxycarbonylethyl, and 1-t-amyl- oxycarbon
  • Examples of the ⁇ (C1-C4 alkoxy) C1-C4 alkoxy ⁇ carbonyl alkyl represented by R 1 1 and R 12 include methoxymethoxy carbonylmethyl and 1-methoxy- methoxycarbonylethyl.
  • Examples of the C- -C6 alkyl represented by R 13 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, and isoamyl.
  • Examples of the Cj-C ⁇ haloalkyl represented by R 13 include 2,2,2-trifluoro- ethyl, chloromethyl, trichloromethyl, and bromomethyl.
  • Examples of the C3-C7 cycloalkyl represented by R 13 include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • Examples of the Cj-C ⁇ alkyl represented by R 14 and R 15 include methyl, ethyl, propyl, butyl, and isopropyl.
  • Examples of the -C6 haloalkyl represented by R 14 and R 15 include trifluoromethyl, 2,2,2-trifluoroethyl, 2-chloroethyl, chloromethyl, and trichloromethyl.
  • Examples of the phenyl optionally substituted by methyl or nitro, which is represented by R 14 and R 15 , include phenyl, p-methylphenyl, 2-nitrophenyl, 3-nitro- phenyl, and 4-nitrophenyl.
  • Examples of the C ⁇ -C ⁇ alkyl represented by R 1 6 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, t-butyl, isoamyl, and t-amyl.
  • haloalkyl represented by R 16 examples include chloromethyl, dichloromethyl, bromomethyl, dibromomethyl, 1-chloroethyl, 1,1-dichloroethyl, 1-bromoethyl, and 1 ,1-dibromoethyl.
  • Examples of the C2-C6 alkenyl represented by R 16 include vinyl, allyl, 1-propenyl, and l -methyl-2-propenyl.
  • Examples of the C 2 -C6 haloalkenyl represented by R 16 include 3,3-dichloro- 2-propenyl and 3,3-dibromo-2-propenyl.
  • Examples of the C2-C6 alkynyl represented by R 16 include 2-butynyl.
  • Examples of the C2-C6 haloalkynyl represented by R 16 include 3-bromo-2- propynyl.
  • Examples of the C2-C8 alkoxyalkyl represented by R 16 include methoxy- methyl, ethoxymethyl, and isopropoxymethyl.
  • Examples of the hydroxy Cj-C ⁇ alkyl represented by R 16 include hydroxy- methyl.
  • Examples of the C]-C6 alkyl represented by R 17 and R 18 include methyl.
  • Examples of the C 1 -C3 alkyl represented by R 4 include methyl.
  • Examples of the C ⁇ -C , alkyl represented by R 5 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, and isoamyl.
  • Examples of the C--C6 haloalkyl represented by R 5 include 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and bromodifluoromethyl.
  • Examples of the C3-C6 alkenyl represented by R 5 include allyl, l-methyl-2- propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl.
  • Examples of the C3-C6 haloalkenyl represented by R 5 include 2-chloro-2- propenyl and 3,3-dichloro-2-propenyl.
  • Examples of the C3-C6 alkynyl represented by R 5 include propargyl, l-methyl-2-propynyl, 2-butynyl, and l,l-dimethyl-2-propynyl.
  • Examples of the C3-C6 haloalkynyl represented by R 5 include 3-iodo-2- propynyl and 3-bromo-2-propynyl.
  • Examples of the cyano -C6 alkyl represented by R 5 include cyanomethyl.
  • Examples of the C2-C8 alkoxyalkyl represented by R 5 include methoxy- methyl, ethoxymethyl, and 1-methoxyethyl.
  • Examples of the C3-C8 alkoxyalkoxyalkyl represented by R 5 include methoxyethoxymethyl.
  • Examples of the carboxy C1-C6 alkyl represented by R 5 include carboxy- methyl, 1 -carboxyethyl, and 2-carboxyethyl.
  • Examples of the (Cj-Cg alkoxy)carbonyl C ⁇ -C alkyl represented by R 5 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopro ⁇ poxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycar- bonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonyl- methyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1-iso- propoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1 -t-butoxycar- bonylethyl, 1 -amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-amyloxycar
  • Examples of the ⁇ (C1 -C4 alkoxy) C 1 -C 4 alkoxy ⁇ carbonyl alkyl represented by R 5 include methoxymethoxycarbonylmethyl and 1 -methoxymethoxy- carbonylethyl.
  • Examples of the (C3-C8 cycloalkoxy)carbonyl C ⁇ -C alkyl represented by R 5 include cyclobutyloxycarbonylmethyl, cyclopentyloxycarbonylmethyl, cyclohexyloxy- carbonylmethyl, 1 -cyclobutyloxycarbonylethyl, 1 -cyclopentyloxycarbonylethyl, and 1 -cyclohexyloxycarbonylethyl.
  • Examples of the C2-C8 alkylthioalkyl represented by R 5 include methylthio- methyl.
  • Examples of the C ⁇ -C(, alkylsulfonyl represented by R 5 include methane- sulfonyl, ethanesulfonyl, and isopropylsulfonyl.
  • Examples of the Cj-C ⁇ haloalkylsulfonyl represented by R 5 include trifluoro- methanesulfonyl, chloromethanesulfonyl, trichloromethanesulfonyl, 2-chloroethane- sulfonyl, and 2,2,2-trifluoroethanesulfonyl.
  • Examples of the (Cj -Cs alkyl)carbonyl represented by R 5 include acetyl, ethylcarbonyl, propylcarbonyl, and isopropylcarbonyl.
  • Examples of the (Ci-Cs alkoxy)carbonyl represented by R 5 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl, isoamyloxycarbonyl, and t-amyl- oxycarbonyl.
  • hydroxy Ci-C ⁇ alkyl represented by R 5 examples include hydroxy- methyl, hydroxyethyl, and hydroxypropyl.
  • Examples of the Cj-C ⁇ alkyl represented by R 6 include methyl and ethyl.
  • Examples of the C--C6 haloalkyl represented by R 6 include bromomethyl, dibromomethyl, tribromomethyl, 1-bromoethyl, chloromethyl, dichloromethyl, and trichloromethyl.
  • Examples of the hydroxy C--C6 alkyl represented by R 6 include hydroxy- methyl.
  • Examples of the C 1 -C6 alkoxy Cj-C ⁇ alkyl represented by R 6 include methoxymethyl, ethoxymethyl, propoxymethyl, and is opropoxy methyl.
  • Examples of the -C6 alkoxy Cj-C ⁇ alkoxy C ⁇ -CQ alkyl represented by R 6 include methoxymethoxymethyl, methoxyethoxymethyl, and ethoxymethoxy methyl.
  • Examples of the alkyl represented by R 6 include acetyloxymethyl, ethylcarbonyloxymethyl, and isopropylcarbonyloxymethyl.
  • Examples of the (C 1 -C6 haloalkyl)carbonyloxy C--C6 alkyl represented by R 6 include trifluoroacetyloxymethyl, chloroacetyloxymethyl, and trichloroacetyloxy- methyl.
  • Examples of the (C--C6 alkoxy)carbonyl represented by R 6 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, and isoamyloxycarbonyl.
  • Examples of the (Ci-C ⁇ alkyl)carbonyl represented by R 6 include methyl- carbonyl, ethylcarbonyl, and isopropylcarbonyl.
  • Examples of the alkyl represented by R 7 include methyl.
  • Examples of the Cj-C6 alkyl represented by R 8 include methyl and ethyl.
  • Examples of the Cj-C ⁇ haloalkyl represented by R 8 include chloromethyl, bromomethyl, and fluoro methyl.
  • Examples of the Cj-C ⁇ hydroxyalkyl represented by R 8 include hydroxy- methyl.
  • Examples of the C2-C8 alkoxyalkyl represented by R 8 include methoxy- methyl, ethoxymethyl, isopropoxymethyl, butoxymethyl, and isobutoxymethyl.
  • Examples of the C3-C10 alkoxyalkoxyalkyl represented by R 8 include methoxymethoxy methyl, methoxyethoxymethyl, and ethoxymethoxymethyl.
  • Examples of the (C1-C5 alkyl)carbonyloxy -C6 alkyl represented by R 8 include acetyloxymethyl, ethylcarbonyloxymethyl, and isopropylcarbonyloxymethyl.
  • Ci-C ⁇ , haloalkyl)carbonyloxy alkyl represented by R 8 examples include chloromethylcarbonyloxymethyl.
  • Examples of the carboxy alkyl represented by R 8 include carboxy- methyl.
  • Examples of the (C ⁇ -C8)alkoxycarbonyl represented by R 8 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, and isoamyloxycarbonyl.
  • Examples of the (Cj-C6 haloalkoxy)carbonyl represented by R 8 include 2-chloroethoxycarbonyl, 2-bromoethoxycarbonyl, 3-chlorobutoxycarbonyl, l-chloro-2- propoxycarbonyl, l,3-dichloro-2-propoxycarbonyl, 2,2-dichloroethoxycarbonyl, 2,2,2- trifluoroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, and 2,2,2-tribromoethoxy- carbonyl.
  • Examples of the (C3-C10 cycloalkoxy)carbonyl represented by R 8 include cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, and cyclohexyloxycarbonyl.
  • Examples of the (C3-C8 alkenyloxy)carbonyl represented by R 8 include allyloxycarbonyl and 3-butenyloxycarbonyl.
  • Examples of the (C3-C8 alkynyloxy)carbonyl represented by R 8 include propargyloxycarbonyl, 3-butynyloxycarbonyl, and l-methyl-2-propynyloxycarbonyl.
  • Examples of the (C]-C6 alkyl)aminocarbonyl represented by R 8 include methylaminocarbonyl, ethylaminocarbonyl, and propylaminocarbonyl.
  • Examples of the di(C]-C6 alkyl)aminocarbonyl represented by R 8 include dimethylaminocarbonyl, diethylaminocarbonyl, and diisopropylaminocarbonyl.
  • Examples of the (C ⁇ -C6 alkyl)aminocarbonyloxy Cj-C ⁇ alkyl represented by R 8 include methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, and propyl- aminocarbonyloxy methyl.
  • Examples of the di(C ⁇ -C6 alkyl)aminocarbonyloxy Cj-C6 alkyl represented by R 8 include dimethylaminocarbonyloxyalkyl and diethylaminocarbonyloxyalkyl.
  • R 1 is preferably hydrogen
  • R 2 is preferably C 1 -C3 alkyl substituted with one or more halogen atoms, more preferably methyl substituted with one or more fluorine atoms, or ethyl substituted with one or more fluorine atoms, and most preferably trifluoromethyl;
  • R 3 is preferably methyl or ethyl, more preferably methyl
  • Q is preferably [Q-l], [Q-2], [Q-3], or [Q-4];
  • Y is preferably halogen
  • Z 1 is preferably oxygen or sulfur
  • Z 2 is preferably oxygen
  • B is preferably hydrogen, nitro, -OR 1 0 , -SR 1 0 , -NHR 10 , -NHSO 2 R 14 , -COOR 13 , or -CH 2 CHWCOOR 13 .
  • W is preferably hydrogen or chlorine
  • R 10 is preferably C ⁇ -C(, alkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, cyano -C6 alkyl, or ( -C6 alkoxy)carbonyl C 1 -C6 alkyl
  • R 13 is preferably C 1 -C6 alkyl
  • R 14 is preferably C1-C6 alkyl;
  • R 5 is preferably Cj-C6 alkyl, C3-C6 alkenyl, or C3-C6 alkynyl;
  • R 6 is preferably Cj-C ⁇ alkyl, Cj -C ⁇ haloalkyl, formyl, hydroxymethyl, C]-C6 alkoxymethyl, C 1 -C6 alkylcarbonyloxymethyl, or C]-C6 alkoxycarbonyl;
  • R 7 is preferably hydrogen or methyl; and R 8 is preferably methyl, hydroxymethyl, CJ-CO alkoxymethyl, (C1-C5 alkyl)- carbonyloxymethyl, carboxyl, or (C]-C6 alkoxy)carbonyl.
  • Preferred examples of the present compounds from the viewpoint of their herbicidal activity are those which contain the above preferred substituents in combina ⁇ tion.
  • R 2 is methyl substituted with one or more fluorine atoms, or ethyl substituted with one or more fluorine atoms.
  • more preferred compounds are those wherein B is -OR 10 or -NHR 1 0 .
  • R 10 is C3-C6 alkynyl or (Ci-C ⁇ alkoxy)carbonyl C--C6 alkyl; or when B is -NHR 10 , then R 10 is alkyl.
  • R 10 is C3-C 4 alkynyl, (Cj-Cg alkoxy)carbonylmethyl, or 1-(C* -C6 alkoxy)carbonylethyl.
  • R 1 is hydrogen; R 3 is methyl; X is fluorine; and Y is chlorine.
  • Q is [Q-2]
  • more preferred compounds are those wherein Z 1 is oxygen; n is 1 ; R 4 is hydrogen; and R 5 is C3-C6 alkynyl.
  • R 5 is C3-C4 alkynyl.
  • R 1 is hydrogen; R 3 is methyl; and X is fluorine.
  • Particularly preferred compounds are those wherein R 1 is hydrogen; R 2 is trifluoromethyl; R 3 is methyl; Q is [Q-l]; X is fluorine; Y is chlorine; and B is propargyloxy; those wherein R 1 is hydrogen; R 2 is trifluoromethyl; R 3 is methyl; Q is [Q-l]: X is fluorine; Y is chlorine: and B is l-(ethoxycarbonyl)ethoxy; those wherein R 1 is hydrogen; R 2 is trifluoromethyl; R 3 is methyl; Q is [Q- l]; X is fluorine; Y is chlorine; and B is l-(methoxycarbonyl)ethoxy; and those wherein R 1 is hydrogen; R 2 is trifluoromethyl; R 3 is methyl; Q is [Q-2]; X is fluorine; Z 1 is oxygen; n is 1 ; R 4 is hydrogen; and R 5 is propargyl.
  • Some of the present compounds have optical isomers based on the presence of at least one asymmetric carbon atom, and all of the optical isomers are, of course, included within the scope of the present invention.
  • the present compounds can be produced by various production processes as described below.
  • R 1 , R 2 , R 3 , Q, and D are as defined above.
  • the reaction is usually effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 100°C.
  • the reaction time is usually in the range of a moment to 96 hours.
  • the amounts of the reagents to be used in the reaction are usually 1 to 5 moles of compound [3] and usually 1 mole to an excess of the base, per mole of compound [2],
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethyl- formamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropyl- ethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; sulfur compounds such as dimethylsulfoxide and sulforane; alcohols such as methanol, ethanol,
  • Examples of the base used in the reaction include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- efhylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate
  • organic bases such as triethylamine, diisopropyl- efhylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • reaction mixture After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato- graphy or recrystallization.
  • a technique such as chromato- graphy or recrystallization.
  • R 1 , R 2 , and R 3 are as defined above, may be formed as a by-product and can be isolated in the same manner as in the isolation of the above present compound.
  • Some of the compounds [7] have herbicidal activity.
  • R 22 is C--C6 alkyl
  • R 51 is a substituent other than hydrogen, which is included in the definition of R 5
  • R 1 , R 2 , R 3 , R 4 , and X are as defined above.
  • Compound [1-2] can be produced by reacting compound [1-1] with a nitrating agent in a solvent.
  • Nitrating agent nitric acid or the like
  • Amount of nitrating agent 1 to 10 moles per mole of compound [1-1]
  • Solvent sulfuric acid or the like
  • Compound [1-3] can be produced by reacting compound [1-2] with a compound of the formula:
  • Amount of potassium fluoride 1 to 50 moles per mole of compound [ 1 -2]
  • Compound [1-4] can be produced by reducing compound [1-3] with iron powder in the presence of an acid in a solvent.
  • Acid acetic acid or the like
  • Amount of acid 1 to 10 moles
  • Solvent water, ethyl acetate, or the like
  • Compound [ 1-5] can be produced by reacting compound [1 -4] with a compound of the formula:
  • R 51 and D are as defined above.
  • the reaction is usually effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 48 hours.
  • the amounts of the reagents to be used in the reaction are usually 1 to 3 moles of compound [9] and usually 1 to 5 moles of the base, per mole of compound [1 -4].
  • Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate
  • organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro- benzene and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitro ⁇ benzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethyl- amine, N,N-diethylaniline, and N-methylmorpholine; ketones such as acetone and methyl iso
  • the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as column chromatography or recrystallization.
  • a technique such as column chromatography or recrystallization.
  • Compound [1-7] can be produced by reacting compound [1-6] with a compound of the formula:
  • R 4 and R 22 are as defined above, in the presence of a base in a solvent.
  • Base sodium hydride, potassium carbonate, or the like
  • Amount of base 1 to 5 moles per mole of compound [1-6]
  • Compound [1-3] can be produced by reacting compound [1-7] with a nitrating agent in a solvent.
  • Nitrating agent nitric acid or the like
  • Amount of nitrating agent 1 to 10 moles per mole of compound [1-7]
  • Solvent sulfuric acid, acetic acid, or the like
  • Compound [ 1-8] can be produced by reacting compound [1-6] with a nitrating agent in a solvent.
  • Nitrating agent nitric acid or the like
  • Amount of nitrating agent 1 to 10 moles per mole of compound [1-6]
  • Solvent sulfuric acid, acetic acid, or the like
  • Compound [1-3] can be produced by reacting compound [1-8] with compound [10] in the presence of a base in a solvent.
  • Base sodium hydride, potassium carbonate, or the like
  • Amount of base 1 to 5 moles per mole of compound [1-8]
  • Compound [1-10] can be produced by reducing compound [1-9] with iron powder in the presence of an acid in a solvent.
  • Acid acetic acid or the like
  • Amount of acid 1 to 10 moles per mole of compound [1-9]
  • Solvent water, ethyl acetate, or the like
  • Compound [1-1 1] can be produced by reacting compound [1 -10] with sodium thiocyanate, potassium thiocyanate, or the like in a solvent, and then reacting it with bromine or chlorine in a solvent.
  • Amount of sodium thiocyanate, potassium thiocyanate, or the like 1 to 10 moles per mole of compound [1-10]
  • Solvent aqueous hydrochloric acid, aqueous acetic acid, aqueous sulfuric acid, or the like
  • Compound [1-12] can be produced by 1) reacting compound [1-1 1 ] with sodium nitrite, potassium nitrite, or the like in a solvent, and then 2) heating it in an acidic solution.
  • Amount of sodium nitrite, potassium nitrite, or the like 1 to 2 moles per mole of compound [1-11]
  • Solvent aqueous hydrochloric acid or aqueous sulfuric acid
  • Acidic solution aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Compound [1- 13] can be produced by reacting compound [1-12] with compound [9] in the presence of a base in a solvent.
  • Base sodium hydride, potassium carbonate, or the like
  • Amount of base 1 to 10 moles per mole of compound [1-12]
  • Compound [1-15] can be produced by reducing compound [1-14] with iron powder in the presence of an acid in a solvent.
  • Acid acetic acid or the like
  • Amount of acid 1 to 10 moles per mole of compound [1-14]
  • Solvent water, ethyl acetate, or the like
  • Compound [1-16] can be produced by 1) reacting compound [1-15] with a nitrite salt in a solvent to form a diazonium salt, and then 2) raising the temperature to cause the cyclization of the diazonium salt in a solvent.
  • Nitrite salt sodium nitrite, potassium nitrite, or the like
  • Amount of nitrite salt 1 to 2 moles per mole of compound [1-15]
  • Solvent aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Solvent aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Y 1 is a substituent other than nitro, which is included in the definition of Y;
  • R 101 is a substituent other than hydrogen, which is included in the definition of R 10 ; and
  • X, R 1 , R 2 , and R 3 are as defined above.
  • Compound [1-18] can be produced by reacting compound [1-17] with a nitrating agent in a solvent.
  • Nitrating agent nitric acid or the like
  • Amount of nitrating agent 1 to 10 moles per mole of compound [1-17]
  • Solvent sulfuric acid or the like
  • Compound [1-19] can be produced by reducing compound [1-18] with iron powder in the presence of an acid in a solvent.
  • Acid acetic acid or the like
  • Amount of acid 1 to 10 moles per mole of compound [1-18]
  • Solvent water, ethyl acetate, or the like
  • Compound [1-20] can be produced by 1) reacting compound [1-19] with a nitrite salt in a solvent, and then 2) heating it in an acid solution.
  • Nitrite salt sodium nitrite, potassium nitrite, or the like
  • Amount of nitrite salt 1 to 2 moles per mole of compound [1-19]
  • Solvent aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Acidic solution aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Compound [1 -21] can be produced by reacting compound [1-20] with a compound of the formula:
  • R 101 and D are as defined above.
  • the reaction is usually effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 48 hours.
  • the amounts of the reagents to be used in the reaction are usually 1 to 3 moles of compound [11] or [12] and usually 1 to 5 moles of the base, per mole of compound [1-20].
  • Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate
  • organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro- benzene and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitro ⁇ benzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylefhylamine, N,N-dimethyl- amine, N,N-diethylaniline, and N-methylmorpholine; ketones such as acetone and methyl is
  • the above compound [1-20] can also be produced by the following process:
  • Compound [1-20] can be produced by deprotecting compound [1-22] in the presence of hydrogen bromide-acetic acid or sulfuric acid without any solvent or in a solvent
  • Solvent sulfuric acid, acetic acid, or the like
  • R 23 and R 24 are independently a substituent included in the definition of R 1 1 or R 12 ; or -COR 13 , -SO 2 R 14 , -SO 2 R 15 , or -COOR 13 , wherein R 13 , R 14 , and R 15 are as defined above; X, Y 1 , R 1 , R 2 , and R 3 are as defined above.
  • Compound [1-23] can be produced by reacting compound [1-19] with a compound of the formula:
  • R 23 and D are as defined above, in the presence or absence of a base without any solvent or in a solvent.
  • Base organic bases such as pyridine and triethylamine; and inorganic bases such as potassium carbonate
  • Amount of base 1 to 3 moles per mole of compound [1-19]
  • Compound [ 1 -24] can be produced by reacting compound [1-23] with a compound of the formula:
  • R 24 and D are as defined above, in the presence or absence of a base without any solvent or in a solvent.
  • Base organic bases such as pyridine and triethylamine; and inorganic bases such as potassium carbonate
  • Amount of base 1 to 3 moles per mole of compound [ 1 -23]
  • Compound [1-25] can be produced by 1 ) reacting compound [1-19] with a nitrite salt in a solvent, and then 2) reacting it with potassium xanthate in a solvent. ⁇ Reaction 1)>
  • Nitrite salt sodium nitrite, potassium nitrite, or the like Amount of nitrite salt: 1 to 2 moles per mole of compound [1-19] Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Amount of potassium xanthate 1 to 2 moles per mole of compound [1-19]
  • Solvent aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • Compound [1-26] can be produced by hydrolyzing compound [1-25] in the presence of a base in a solvent.
  • Base inorganic bases such as potassium carbonate
  • Amount of base 1 to 5 moles per mole of compound [ 1 -25]
  • Solvent alcohols such as methanol and ethanol, or the like
  • Compound [ 1-27] can be produced by reacting compound [ 1 -26] with compound [ 1 1 ] or [ 12] in the presence of a base in a solvent.
  • Base inorganic bases such as potassium carbonate; and organic bases such as triethylamine and pyridine
  • Amount of base 1 to 3 moles per mole of compound [ 1 -26]
  • Solvent 1 ,4-dioxane, N,N-dimethylforrnamide, or the like
  • Temperature 0° to 100°C Time: a moment to 24 hours
  • Compound [1-26] can also be produced by the method according to the
  • Compound [1-28] can be produced by reacting compound [1-17] with chlorosulfonic acid without any solvent or in a solvent.
  • Compound [1-26] can be produced by reducing compound [1-28] in a solvent.
  • Reducing agent zinc, tin chloride, or the like
  • Amount of reducing agent 3 moles to an excess per mole of compound
  • Solvent aqueous acetic acid, aqueous hydrochloric acid, aqueous sulfuric acid, or the like
  • R 241 is bromine or iodine; and X, Y 1 , R 1 , R 2 , R 3 , and R 13 are as defined above.
  • Compound [1-29] can be produced by 1) making a diazonium salt from compound [1-19] in a solvent, and then 2) reacting it with potassium iodide or copper
  • Diazotizing agent sodium nitrite, potassium nitrite, or the like Amount of diazotizing agent: 1 to 2 moles per mole of compound [1-19] Solvent: aqueous hydrogen bromide, aqueous hydrogen chloride, aqueous sulfuric acid, or the like
  • Solvent aqueous hydrogen bromide, water, or the like
  • Compound [1-30] can be produced by reacting compound [1-29] with a compound of the formula:
  • R 13 is as defined above, in the presence of a transition metal catalyst and a base in a solvent under an atmosphere of carbon monoxide.
  • Amount of catalyst catalytic amount to 0.5 mole per mole of compound
  • Amount of base 1 to 10 moles per mole of compound [ 1 -29]
  • Atmospheric pressure of carbon monoxide 1 to 150 at
  • R 131 is an substituent other than hydrogen, which is included in the definition of R 13 ; and X, Y 1 , R 1 , R 2 , R 3 , and R 18 are as defined above.
  • Compound [1-31] can be produced by reacting compound [1-29] with sodium formate or potassium formate in the presence of a transition metal catalyst in a solvent under an atmosphere of carbon monoxide.
  • Amount of sodium formate or potassium formate 1 mole to an excess per mole of compound [1-29]
  • Amount of catalyst catalytic amount to 0.5 mole per mole of compound
  • R 18 and R 131 are as defined above, in a solvent, and if compound [19] is used, in the presence of a base.
  • Amount of compound [ 18] or [ 19] 1 to 5 moles per mole of compound
  • Solvent tetrahydrofuran, toluene, or the like
  • Amount of base 1 to 5 moles per mole of compound [1-31]
  • R 171 is C]-C 6 alkyl; and X, Y 1 , R 1 , R 2 , R 3 , R 18 , and R 131 are as defined above.
  • Compound [1-33] can be produced by reacting compound [1-31] with a compound of the formula:
  • R 171 is as defined above, in a solvent.
  • Solvent ether solvents such as tetrahydrofuran
  • Compound [1-34] can be produced by subjecting compound [1-33] to oxida- tive treatment using chromium (VI) oxide-sulfuric acid, pyridinium chlorochromate, or the like; oxidation using dimethylsulfoxide-acetic anhydride; or Swern oxidation.
  • chromium (VI) oxide-sulfuric acid pyridinium chlorochromate, or the like
  • oxidation using dimethylsulfoxide-acetic anhydride or Swern oxidation.
  • R 18 and R 131 are as defined above, in a solvent, and if compound [19] is used, in the presence of a base.
  • Solvent tetrahydrofuran, toluene, or the like
  • Amount of base 1 to 5 moles per mole of compound [ 1 -34]
  • W 2 is chlorine or bromine; and X, Y 1 , R 1 , R 2 , R 3 , and R 13 are as defined above.
  • Compound [1-36] can be produced by reacting compound [1-19] with t-butyl nitrite or t-amyl nitrite; a compound of the formula:
  • R 13 is as defined above, in a solvent.
  • Amount of t-butyl nitrite or t-amyl nitrite 1 to 2 moles per mole of compound [1-19]
  • Compound [1-37] can be produced by reacting compound [1-28] with a compound of the formula:
  • R 10 is as defined above, in the presence of a base without any solvent or in a solvent.
  • Amount of compound [24] 1 mole to an excess per mole of compound [ 1-28]
  • Base organic bases such as triethylamine; and inorganic bases such as potassium carbonate
  • Amount of base 1 to 3 moles per mole of compound [ 1 -28]
  • Compound [1 -38] can be produced by reacting compound [1-28] with a compound of the formula:
  • R 1 ' and R 12 are as defined above, in the presence or absence of a base without any solvent or in a solvent.
  • Base organic bases such as triethylamine; and inorganic bases such as potassium carbonate
  • Amount of base 1 to 3 moles per mole of compound [ 1 -28]
  • R 61 is a substituent other than methyl, which is included in the definition of R 6 ; and X, Y, R 1 , R 2 , and R 3 are as defined above.
  • Compound [1-40] can be produced by reacting compound [1-39] with 2,3-dichloropropene in the presence of a base in a solvent.
  • Base inorganic bases such as potassium carbonate
  • Amount of base 1 to 5 moles per mole of compound [ 1 -39]
  • Compound [1-41] can be produced by heating compound [1-40] in a solvent.
  • Compound [1-42] can be produced from compound [1-41] according to the method in which the methyl group in position 2 on the benzofuran ring is replaced with another substituent, as described in USP 5,308,829, columns 2-11.
  • Compound [1-43] can be produced by reacting compound [1-39] with a compound of the formula:
  • Amount of compound [26] 1 to 5 moles per mole of compound [1-39]
  • Base inorganic bases such as potassium carbonate Amount of base: 1 to 5 moles per mole of compound [1-39]
  • Compound [1-44] can be produced by heating compound [1-43] in a solvent.
  • Compound [1-45] can be produced by heating compound [1-44] in the presence of an acid in a solvent.
  • Acid organic acids such as p-toluenesulfonic acid; and inorganic acids such as sulfuric acid
  • Amount of acid catalytic amount to 1 mole per mole of compound [1-44]
  • Solvent toluene, xylene, or the like
  • R 81 is a substituent other than methyl and hydroxy methyl, which is included in the definition of R 8 ; and X, Y, R 1 , R 2 , R 3 , and R 7 are as defined above.
  • Compound [1-46] can be produced by reacting compound [1-44] with a peracid in a solvent.
  • Peracid m-chloroperbenzoic acid, peracetic acid, or the like Amount of peracid: 1 mole to an excess per mole of compound [1-44] Solvent: halogenated hydrocarbons such as dichloromethane; or organic acids such as acetic acid
  • Compound [ 1-47] can be produced by reacting compound [1-46] in the presence of a base in a solvent.
  • Amount of base 1 to 2 moles per mole of compound [ 1 -46]
  • Solvent methanol, ethanol, or the like Temperature: 0° to 50°C
  • Compound [1 -48] can be produced from compound [1-47] according to the method in which the hydroxyalkyl group in position 2 on the dihydrobenzofuran ring is replaced with another substituent, as described in USP 5,411,935, columns 5-10.
  • Compound [2] which is an intermediate compound for the production of the present compounds, can be produced with high efficiency by reacting compound [5] with compound [6] (hereinafter referred to as intermediate production process 1).
  • the reaction is effected without any solvent or in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 240 hours.
  • the amounts of the reagents to be used in the reaction although the propor ⁇ tion of 1 mole of compound [6] to 1 mole of compound [5] is ideal, can be freely changed depending upon the reaction conditions.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro ⁇ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline,
  • reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, or purified by a technique such as column chromatography or recrystallization.
  • ordinary post-treatments such as extraction with an organic solvent and concentration, or purified by a technique such as column chromatography or recrystallization.
  • purified by a technique such as column chromatography or recrystallization.
  • compound [6] can be replaced with a salt of compound [6] with an organic or inorganic acid (e.g., acetamidine hydrochlo- ride).
  • the reaction is usually effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 240 hours.
  • the amounts of the compounds to be used in the reaction although the proportion of 1 mole of compound [6] to 1 mole of compound [5] is ideal, can be freely changed depending upon the reaction conditions.
  • the amount of the base is usually 1 mole to a large excess per mole of the salt of compound [6].
  • Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate
  • organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro ⁇ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline
  • reaction mixture After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato ⁇ graphy or recrystallization.
  • a technique such as chromato ⁇ graphy or recrystallization.
  • Compound [2] can also be produced by reacting a compound of the formula:
  • the reaction is effected without any solvent or in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 48 hours.
  • the amounts of the reagents to be used in the reaction although the propor ⁇ tion of 1 mole of compound [6] to 1 mole of compound [27] is ideal, can be freely changed depending upon the reaction conditions.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro ⁇ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylfo ⁇ namide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-di
  • reaction mixture After completion of the reaction, the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, or under certain circumstances, the reaction mixture is purified by a technique such as chromatography or recrystallization. Thus the desired compound can be isolated.
  • compound [6] can be replaced with a salt of compound [6] with an organic or inorganic acid (e.g., acetamidine hydrochlo- ride).
  • the reaction is usually effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C.
  • the reaction time is usually in the range of a moment to 72 hours.
  • the amounts of the compounds to be used in the reaction although the proportion of 1 mole of compound [6] to 1 mole of compound [27] is ideal, can be freely changed depending upon the reaction conditions.
  • the amount of the base is usually 1 mole to a large excess per mole of the salt of compound [6].
  • Examples of the base which can be used include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropylethylamine, pyridine, 4-dimethyl- aminopyridine, N,N-dimethylaniline, and N,N-diethylaniline.
  • inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate
  • organic bases such as triethylamine, diisopropylethylamine, pyridine, 4-dimethyl- aminopyridine, N,N-dimethylaniline, and N,N-diethylaniline.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro ⁇ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as fo ⁇ namide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethyl
  • reaction mixture After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato ⁇ graphy or recrystallization.
  • a technique such as chromato ⁇ graphy or recrystallization.
  • Compound [6] can be obtained from commercial sources or can be produced by the method as described in J. Am. Chem. Soc, 78, 6032 (1956).
  • Compound [5] can be produced, for example, by any of the following methods 1 to 4.
  • R 20 and D are as defined above.
  • the reaction can be effected in the presence of a base in a solvent.
  • the reaction temperature is usually in the range of 0° to 100°C.
  • the reaction time is usually in the range of a moment to 48 hours.
  • Examples of the base which can be used include inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, and sodium hydride.
  • Compound [28] includes methyl iodide, methyl bromide, ethyl iodide, ethyl bromide, and isopropyl iodide.
  • the amounts of the reagents to be used in the reaction are usually 1 mole to a large excess of the base and usually 1 to 5 moles of compound [28], per mole of compound [27].
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro ⁇ carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; and mixtures thereof.
  • aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether
  • aromatic hydro ⁇ carbons such as
  • reaction mixture After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato ⁇ graphy or recrystallization.
  • a technique such as chromato ⁇ graphy or recrystallization.
  • R 20 is as defined above, in the presence of an acid catalyst (e.g., p-toluene ⁇ sulfonic acid).
  • an acid catalyst e.g., p-toluene ⁇ sulfonic acid.
  • Q, R 1 , R 19 , and R 20 are as defined above; and G is chlorine, bromine, or iodine.
  • reaction conditions in the respective steps are described, for example, in JP-A 61-106538/1986.
  • R 1 and R 22 are as defined above, in the presence of an appropriate base.
  • the reaction is usually effected in a solvent.
  • the reaction temperature is usually in the range of -20° to 150°C.
  • the reaction time is usually in the range of a moment to 72 hours.
  • the amounts of the compounds to be used in the reaction are usually 1 to 10 moles of compound [37] and usually 1 to 20 moles of the base, per mole of compound [34].
  • Examples of the base which can be used include inorganic bases such as sodium hydride and potassium hydride.
  • solvent examples include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro- carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; and mixtures thereof.
  • aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether
  • aromatic hydro- carbons such as
  • reaction mixture is poured into water and made acidic by the addition of a mineral acid such as hydrochloric acid or sulfuric acid, followed by ordinary post-treatments such as extraction with an organic solvent and concentration, and if necessary, subsequent purification by a technique such as chromato ⁇ graphy or recrystallization.
  • a mineral acid such as hydrochloric acid or sulfuric acid
  • Compound [34] is commercially available, or when the corresponding phenyl- acetic acid (i.e., QCH2COOH) is commercially available, compound [34] can be produced by esterifying this phenylacetic acid according to the ordinary method. However, when neither compound [34] nor the corresponding phenylacetic acid is commercially available, they can be produced, for example, by the following scheme:
  • step a - 4 (step a - 5 )
  • step a - 6 (step a - 7 ) rHz , , H
  • Compound [40] can also be produced by the following scheme: l) NaN0 2 PdCl 2 (PPh 3
  • step a - 9 (step a - 10 )
  • Ph is a phenyl group and Q is as defined above.
  • Step a- 1 can be conducted according to the method as described in Organic Synthesis Collective Volume, 1, 514 (1941);
  • Step a-2 Jikken Kagaku Koza (4th ed.) 21, edited by the Chemical Society of Japan, Maruzen K.K., pp. 89-97;
  • Step a-3 Jikken Kagaku Koza (4th ed.) 20, edited by the Chemical Society of Japan, Maruzen K.K., pp. 1-10;
  • Step a-5 Jikken Kagaku Koza (4th ed.) 20, edited by the Chemical Society of Japan, Maruzen K.K., pp. 10-14;
  • Compound [38] is known in, or can be produced according to the method as described in, EP-61741-A; USP 4,670,046, USP 4,770,695, USP 4,709,049, USP 4,640,707, USP 4,720,927, USP 5,169,431 ; and JP-A 63-156787/1988.
  • R 25 is -COR 26 or -COOR 13
  • R 26 is hydrogen or C--C6 alkyl
  • X and Y 1 are as defined above.
  • the present compounds have excellent herbicidal activity, and some of them exhibit excellent selectivity between crop plants and unfavorable weeds.
  • the present compounds have herbicidal activity against various unfavorable weeds as recited below, which may cause trouble in the foliar treatment and soil treatment on upland fields.
  • Polygonaceae wild buckwheat (Polygonum convolvulus), pale smartweed (Polygonum lapathifolium), Pennsylvania smartweed (Polygonum pensylvanicum), ladysthumb (Poly ⁇ gonum persica ⁇ a), curly dock (Rumex crispus), broadleaf dock (Rumex obtusifolius), Japanese knotweed (Polygonum cuspidatum)
  • Portulacaceae common purslane (Portulaca oleracea)
  • Caryophyllaceae common chickweed (Stella ⁇ a media) Chenopodiaceae: common lambsquarters (Chenopodium album), kochia (Kochia scoparia) Amaranthaceae: redroot pigweed (Amaranthus retroflexus), smooth pigweed (Amaranthus hyb ⁇ dus) Crusiferae: wild radish (Raphanus raphanistrum), wild mustard (Sinapis arvensis
  • some of the present compounds have no problematic phyto- toxicity on main crops such as com (Zea mays), wheat (Triticum aestivum), barley (Hordeum vulgare), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), cotton (Gossypium spp.), sugar beet (Beta vulgaris), peanut (Arachis hypogaea), sunflower (Helianthus annuus) and canola (Brassica napus); garden crops such as flowers and ornamental plants; and vegetable crops.
  • com Zinc
  • wheat Triticum aestivum
  • barley Hydeum vulgare
  • rice Oryza sativa
  • sorghum Sorghum bicolor
  • soybean Glycine max
  • cotton Gossypium spp.
  • sugar beet Beta vulgaris
  • peanut Arachis hypogaea
  • sunflower Helianthus annuus
  • canola Brassica
  • the present compounds can attain effective control of unfavorable weeds in the no-tillage cultivation of soybean (Glycine max), com (Zea mays), and wheat (Triticum aestivum). Furthermore, some of them exhibit no problematic phytotoxicity on crop plants.
  • the present compounds have herbicidal activity against various unfavorable weeds as recited below under the flooding treatment on paddy fields.
  • Gramineae barnyardgrass (Echinochloa oryzicola) Scrophulariaceae: common falsepimpemel (Lindernia procumbens) Lythraceae:
  • Cyperaceae smallflower umbrellaplant (Cyperus difformis), hardstem bulrush (Scirpus juncoides), needle spikerush (Eleocharis acicularis), Cyperus serotinus, Eleocharis kuroguwai Pontederiaceae:
  • the present compounds can attain effective control of various unfavorable weeds in orchards, grasslands, lawns, forests, waterways, canals, or other non- cultivated lands.
  • the present compounds also have herbicidal activity against various aquatic plants such as water hyacinth (Eichhornia crassipes), which will grow in waterways, canals, or the like.
  • the present compounds have substantially the same characteristics as those of the herbicidal compounds described in the publication of International Patent Application WO95/34659.
  • the present compounds can be used at greater doses than those used when ordinary crop plants without tolerance are cultivated, and it is, therefore, possible to attain effective control of other unfavorable plants.
  • the present compounds When used as active ingredients of herbicides, they are usually mixed with solid or liquid carriers or diluents, surfactants, and other auxiliary agents to give formulations such as emulsifiable concentrates, wettable powders, flowables, granules, concentrated emulsions, and water-dispersible granules.
  • formulations may contain any of the present compounds as an active ingredient at an amount of 0.001 % to 80% by weight, preferably 0.005% to 70% by weight, based on the total weight of the formulation.
  • the solid carrier or diluent may include fine powders or granules of the following materials: mineral matters such as kaolin clay, attapulgite clay, bentonite, terra alba, pyrophyllite, talc, diatomaceous earth, and calcite; organic substances such as walnut shell powder; water-soluble organic substances such as urea; inorganic salts such as ammonium sulfate; and synthetic hydrated silicon oxide.
  • mineral matters such as kaolin clay, attapulgite clay, bentonite, terra alba, pyrophyllite, talc, diatomaceous earth, and calcite
  • organic substances such as walnut shell powder
  • water-soluble organic substances such as urea
  • inorganic salts such as ammonium sulfate
  • synthetic hydrated silicon oxide synthetic hydrated silicon oxide
  • liquid carrier or diluent may include aromatic hydrocarbons such as methylnaphthalene, phenylxylylethane, and alkylbenzenes (e.g., xylene); alcohols such as isopropanol, ethylene glycol, and 2-ethoxyethanol; esters such as phthalic acid dialkyl esters; ketones such as acetone, cyclohexanone, and isophorone; mineral oils such as machine oil; vegetable oils such as soybean oil and cotton seed oil; dimethylsulfoxide, N,N-dimethylformamide, acetonitrile, N-methylpyrrolidone, water, and the like.
  • aromatic hydrocarbons such as methylnaphthalene, phenylxylylethane, and alkylbenzenes (e.g., xylene); alcohols such as isopropanol, ethylene glycol, and 2-ethoxyethanol; esters such as phthalic acid dialkyl esters; keto
  • Examples of the surfactant used for emulsification, dispersing, or spreading may include surfactants of the anionic type, such as alkylsulfates, alkylsulfonates, alkylarylsulfonates, dialkylsulfosuccinates, and phosphates of polyoxyethylene alkyl aryl ethers; and surfactants of the nonionic type, such as polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters.
  • surfactants of the anionic type such as alkylsulfates, alkylsulfonates, alkylarylsulfonates, dialkylsulfosuccinates, and phosphates of polyoxyethylene alkyl aryl ethers
  • surfactants of the nonionic type such as polyoxyethylene alkyl
  • auxiliary agent used for formulation may include lignin- sulfonates, alginates, polyvinyl alcohol, gum arabic, carboxymethyl cellulose (CMC), and isopropyl acid phosphate (PAP).
  • the present compounds are usually formulated as described above and then used for the pre- or post-emergence soil, foliar, or flooding treatment of unfavorable weeds.
  • the soil treatment may include soil surface treatment and soil incorporation.
  • the foliar treatment may include application over the plants and directed application in which a chemical is applied only to the unfavorable weeds so as to keep off the crop plants.
  • the present compounds can be used, if necessary, in combination with other compounds having herbicidal activity.
  • Examples of the compounds which can be used in combination with the present compounds may include various compounds described in Catalog 1995 Edition of Farm Chemicals Handbook (Meister Publishing Company); AG CHEM NEW COMPOUND REVIEW, VOL. 13, 1995 (AG CHEM INFORMATION SERVICE); JOSOUZAI KENKYU SOURAN (Hakuyu-sha); or HERBICIDE HAND ⁇ BOOK Seven Edition (Weed Science Society of America).
  • Typical examples of such compounds are as follows: atrazin, cyanazine, dimethametryn, metribuzin, prometryn, simazine, simetryn, chlorotoluron, diuron, dymuron, fluometuron, isoproturon, linuron, methabenzthiazuron, bromoxynil, ioxynil, ethalfluralin, pendimethalin, trifluralin, acifluorfen, acifluorfen-sodium, bifenox, chlomethoxynil, fomesafen, lactofen, oxadiazon, oxyfluorfen, carfentrazone, flumiclorac-pentyl, flumioxazine, fluthiacet- methyl, sulfentrazone, thidiazimin, difenzoquat, diquat, paraquat, 2,4-D, 2,4-DB, DCPA, MCPA,
  • the present compounds may be used in combination with other herbicides to enhance their herbicidal activity.
  • the present compounds can also be used in combination with insecticides, acaricides, nematocides, fungicides, plant growth regulators, fertilizers, soil improver, or the like.
  • the application amount is usually in the range of 0.01 to 10,000 g, preferably 1 to 8000 g, per hectare, although it may vary depending upon the weather conditions, formulation type, application timing, application method, soil conditions, crop plants, unfavorable weeds, and the like.
  • the formulation is usually applied at a prescribed amount after diluted with water having a volume of about 10 to 1000 liters per hectare, if necessary, with the addition of an adjuvant such as a spreading agent.
  • the formulation is usually applied as such without any dilution.
  • Examples of the adjuvant used may include, in addition to the surfactants recited above, polyoxyethylene resin acids (esters), ligninsulfonates, abietates, dinaphthylmethanedisulfonates, crop oil concentrates, and vegetable oils such as soybean oil, corn oil, cotton seed oil, and sunflower oil.
  • the present compounds can also be used as active ingredients of harvesting aids such as defoliants and desiccating agents for cotton, and desiccating agents for potato.
  • the present compounds are usually formulated in the same manner as the case where they are used as active ingredients of herbicides, and used alone or in combination with other harvesting aids for foliar treatment before the harvesting of crops.
  • CH 2 CC1 CH 2 CH 2 C ⁇ CH CH(CH 3 )C ⁇ CH CH 2 CN CH 2 OCH 3 CH 2 0C 2 H s CH 2 COOH CH 2 COOCH 3 CH 2 C00C 2 H s CH 2 C00 " C 3 H 7 CH 2 C00 n C 4 H 9 CH 2 C00 " C 5 H ,, CH 2 C00 ⁇ C 3 H 7 CH 2 C00 c C s H a CH 2 C00 c C 6 H , ⁇ CH(CH 3 )C00H CH(CH 3 )COOCH 3 CH(CH 3 )C00C a H s CH(CH 3 )C00 n C 3 H 7 CH(CH 3 )C00" C 4 H 9 CH(CH 3 )C00" C s H i. CH(CH 3 )C00 i C 3 H 7 CH(CH 3 )C00 C C s H 8 TABLE 2 (contn'd)

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Abstract

Novel pyrimidin-4-one derivatives of formula (1) are provided, which are useful as active ingredients of herbicides, wherein R1 is hydrogen or alkyl; R2 is alkyl optionally substituted with halogen; R3 is alkyl optionally substituted with halogen, alkenyl, or alkynyl; and Q is substituted phenyl. Also provided are intermediates for their production and processes for producing these intermediates.

Description

DESCRIPTION
PY IMIDIN-4-0NE DERIVATIVES, THEIR USE AS HERBICIDES, INTERMEDIATES FOR THEIR PRODUCTION AND PROCESSES FOR PRODUCING THESE COMPOUNDS
Technical Field
The present invention relates to pyrimidin-4-one derivatives, their use, inter¬ mediates for their production, and processes for producing these intermediates.
Disclosure of Invention
The present inventors have intensively studied to find a compound having excellent herbicidal activity. As a result, they have found that pyrimidin-4-one deriva¬ tives represented by formula [ 1 ] as depicted below have excellent herbicidal activity, thereby completing the present invention.
Thus the present invention provides a compound of the formula:
wherein R1 is hydrogen or C1-C3 alkyl; R2 is C1-C3 alkyl optionally substituted with one or more halogen atoms; R3 is alkyl optionally substituted with one or more halogen atoms, C3-C6 alkenyl, or C3-C6 alkynyl; and Q is substituted phenyl (herein¬ after referred to as the present compound(s)); and a herbicide containing it as an active ingredient.
The present invention also provides a process for producing compound [ 1 ], which comprises reacting a compound of the formula:
wherein Q, R1, and R2 are as defined above, with a compound of the formula: R3-D [3]
wherein D is chlorine, bromine, iodine, methanesulfonyloxy, trifluoromethanesulfonyl- oxy, or p-toluenesulfonyloxy; and R3 is as defined above.
The present invention further provides a compound of the formula:
wherein Q and R1 are as defined above; R21 is C--C3 alkyl substituted with one or more halogen atoms, which is useful as an intermediate for the production of some of the present compounds; and a process for producing a compound of the formula:
wherein Q, R1, and R2 are as defined above, which comprises reacting a compound of the formula:
wherein R19 and R20 are independently -C3 alkyl, and Q and R1 are as defined above, with a compound of the formula:
HN R2 I«I
H2N
wherein R2 is as defined above. The compound [2] may be present as a compound of the formula:
which is a tautomer thereof.
Examples of Q in the present invention include [Q-l], [Q-2], [Q-3], [Q-4], or [Q-5] of the formula:
wherein X is hydrogen or halogen;
Y is halogen, nitro, cyano, or trifluoromethyl;
Z1 is oxygen, sulfur, NH, or methylene;
Z2 is oxygen or sulfur; n is 0 or 1 ;
B is hydrogen, halogen, nitro, cyano, chlorosulfonyl, -OR10, -SR10, -SO2- OR10, -N(R10)Rπ, -SO2N(Rπ)R12, -NRn(COR 13), -NRH(SO R14), -N(SO2R14)- (SO2R 15), -N(SO2R 14)(COR 13), -NHCOOR 13, -COOR13, -CON(Rπ)R12, -CSN- (Rπ )R 1 2, -COR16, -CR17=CR 18CHO, -CR17=CR18COOR 13, CR17=CR1 8CON- (Rn )R12, -CH2CHWCOOR13, or -CH2CHWCON(Rπ)R12, wherein W is hydrogen, chlorine, or bromine; R10 is hydrogen, -C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, cyano alkyl, C2-Cg alkoxyalkyl, C2-Cs alkylthioalkyl, carboxy alkyl, (C--C6 alkoxy)- carbonyl Cj-Cό alkyl, (C]-C6 haloalkoxy)carbonyl Cj-Cβ alkyl, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl -C6 alkyl, (C3-C8 cycloalkoxy)carbonyl Cj-C6 alkyl, -CH2CON- (Rπ)R12, -CH2COON(Rn)R12, -CH(Cι-C4 alkyDCONCR11^12, or -CH(Cι-C4 alkyl)- COON(Rn)R12; R1 1 and R12 are independently hydrogen, C]-C6 alkyl, Cι-C6 halo¬ alkyl, C3-C6 alkenyl, C3-C6 alkynyl, cyano C1-C6 alkyl, C2-C8 alkoxyalkyl, C2-C8 alkylthioalkyl, carboxy C--C6 alkyl, alkoxy)carbonyl -C6 alkyl, or {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl Cj-Cό alkyl, or R1 1 and R12 are taken together to form tetramethylene, pentamethylene, or ethyleneoxyethylene; R13 is hydrogen, C\-C^ alkyl, Cj -Cό haloalkyl, or C3-C8 cycloalkyl; R 14 and R15 are independently alkyl, C]-C6 haloalkyl, or phenyl optionally substituted with methyl or nitro; R16 is hydrogen, C1-C6 alkyl, haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C8 alkoxyalkyl, or hydroxy alkyl; and R17 and R18 are indepen¬ dently hydrogen or Cj-Cό alkyl;
R4 is hydrogen or C1-C3 alkyl,
R5 is hydrogen, C 1-C6 alkyl, C- -C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, cyano alkyl, C2-C8 alkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, carboxy C1-C6 alkyl, (Ci-Cβ alkoxy)carbonyl C1-C6 alkyl, { (C1-C4 alkoxy) C1-C4 alkoxy} carbonyl Cj-Cό alkyl, (C3-C8 cycloalkoxy)carbonyl- C ι -C6 alkyl, -CH2CON(R u)R 12, -CH2COON(R n)R12, -CH(Cι-C4 alkyl)CON- (Rπ)R12, -CH(Cι-C4 alkyl)COON(Rπ)R12, C2-C8 alkylthioalkyl, Cι-C6 alkylsulfonyl, C]-C6 haloalkylsulfonyl, (C\-C$ alkyl)carbonyl, (Cj-Cs alkoxy)carbonyl, or hydroxy C] -CO alkyl;
R 6 is C 1-C6 alkyl, C\ -C(, haloalkyl, formyl, cyano, carboxyl, hydroxy C ι-C6 alkyl, C] -C6 alkoxy Cι-C6 alkyl, Cι-C6 alkoxy Cι-C6 alkoxy C--C6 alkyl, (C ]-C6 alkyl)carbonyloxy Cj-Cβ alkyl, (Cj-Cό haloalkyl)carbonyloxy Cj-Cό alkyl, (C]-C6 alkoxy)carbonyl, or (C\-C(, alkyl)carbonyl;
R7 is hydrogen or Ci -C alkyl; and
R8 is C ι-C6 alkyl, Cι-C6 haloalkyl, Cι-C6 hydroxyalkyl, C -C8 alkoxy¬ alkyl, C3-C10 alkoxyalkoxyalkyl, (C1-C5 alkyl)carbonyloxy Cj-Cβ alkyl, (Cj-Cό halo- alkyl)carbonyloxy Cj-C6 alkyl, carboxyl, carboxy C- -C6 alkyl, (Cj-Cs alkoxy)- carbonyl, (C--C6 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C8 alkenyl- oxy)carbonyl, (C3-C8 alkynyloxy)carbonyl, aminocarbonyl, ( -C6 alkyl)amino- carbonyl, di(C]-C6 alkyl)aminocarbonyl, (C--C6 alkyl)aminocarbonyloxy C--C6 alkyl, or di(C]-C6 alkyl)aminocarbonyloxy -Cό alkyl.
In the above definition of the present compounds, the respective substituents are exemplified as follows:
Examples of the -C3 alkyl represented by R1 include methyl, ethyl, and isopropyl.
Examples of the C1-C3 alkyl optionally substituted with one or more halogen atoms, which is represented by R2, include methyl, ethyl, isopropyl, trichloromethyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.
Examples of the C--C6 alkyl optionally substituted with one or more halogen atoms, which is represented by R3, include methyl, ethyl, isopropyl, difluoromethyl, and bromodifluoromethyl.
Examples of the C3-C6 alkenyl represented by R3 include allyl and 1-methyl- 2-propenyl.
Examples of the C3-C6 alkynyl represented by R3 include propargyl and 1 -methyl-2-propynyl.
In the formulas [Q- l], [Q-2], [Q-3], [Q-4], and [Q-5], the respective substituents are exemplified as follows:
Examples of the halogen represented by X, Y, and B include chlorine, fluorine, bromine, and iodine. Examples of the Cj -C6 alkyl represented by R10 include methyl, ethyl, isopropyl, propyl, isobutyl, butyl, t-butyl, amyl, isoamyl, and t-amyl.
Examples of the Cj-Cό haloalkyl represented by R10 include difluoromethyl, tetrafluoroethyl, and 2,2,2-trifluoroethyl.
Examples of the C3-C8 cycloalkyl represented by R10 include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
Examples of the C3-C6 alkenyl represented by R10 include allyl, l-methyl-2- propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl.
Examples of the C3-C6 haloalkenyl represented by R10 include 2-chloro-2- propenyl and 3,3-dichloro-2-propenyl.
Examples of the C3-C6 alkynyl represented by R10 include propargyl, 1 -methyl-2-propynyl, 2-butynyl, and l,l-dimethyl-2-propynyl.
Examples of the C3-C6 haloalkynyl represented by R10 include 3-bromo-2- propynyl.
Examples of the cyano -C6 alkyl represented by R10 include cyanomethyl.
Examples of the C2-C8 alkoxyalkyl represented by R10 include methoxy- methyl, methoxyethyl, ethoxymethyl, and ethoxyethyl.
Examples of the C2-C8 alkylthioalkyl represented by R10 include methylthio- methyl.
Examples of the carboxy C--C6 alkyl represented by R10 include carboxy- methyl, 1 -carboxyethyl, and 2-carboxyethyl.
Examples of the (C\-C(, alkoxy)carbonyl -C6 alkyl represented by R10 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopro- poxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycar- bonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonyl- ethyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1-iso- propoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxy- carbonylethyl, 1 -amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-amyloxy- carbonylethyl.
Examples of the (Ci-Cβ haloalkoxy)carbonyl Cj-C6 alkyl represented by R10 include 2,2,2-trifluoroethoxycarbonylmethyl.
Examples of the { (C1 -C4 alkoxy) C1-C4 alkoxy} carbonyl Cj-Cό alkyl represented by R10 include methoxymethoxycarbonylmethyl and 1-methoxymethoxy- carbonylethyl.
Examples of the (C3-C8 cycloalkoxy)carbonyl C1-C6 alkyl represented by R ■ ° include cyclobutyloxycarbonylmethyl, cyclopentyloxycarbonylmethyl, cyclohexyl- oxycarbonylmethyl, 1 -cyclobutyloxycarbonylethyl, 1-cyclopentyloxycarbonylethyl, and 1 -cyclohexyloxycarbonylethyl.
Examples of the C1-C6 alkyl represented by R1 1 and R12 include methyl, ethyl, propyl, butyl, isopropyl, and isobutyl.
Examples of the C--C6 haloalkyl represented by R1 1 and R12 include chloro- ethyl and bromoethyl.
Examples of the C3-C6 alkenyl represented by R1 1 and R12 include allyl, l-methyl-2-propenyl, and 3-butenyl.
Examples of the C3-C6 alkynyl represented by R1 1 and R12 include propargyl and l-methyl-2-propynyl.
Examples of the cyano Ci-Cζ alkyl represented by R 1 1 and R 12 include cyanomethyl.
Examples of the C2-C8 alkoxyalkyl represented by R 1 1 and R 12 include methoxymethyl and ethoxyethyl.
Examples of the C2-Cg alkylthioalkyl represented by R1 1 and R12 include methylthiomethyl and methylthioethyl.
Examples of the carboxy C- -C6 alkyl represented by R1 1 and R 12 include carboxymethyl and 1-carboxyethyl.
Examples of the ( -C6 alkoxy)carbonyl C--C6 alkyl represented by R1 1 and R • 2 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxy- carbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycar- bonylmethyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1 -isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutόxycarbonylethyl, 1-t- butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1 -isoamyloxycarbonylethyl, and 1-t-amyl- oxycarbonylethyl.
Examples of the {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl alkyl represented by R1 1 and R12 include methoxymethoxy carbonylmethyl and 1-methoxy- methoxycarbonylethyl.
Examples of the C- -C6 alkyl represented by R13 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, and isoamyl.
Examples of the Cj-Cβ haloalkyl represented by R13 include 2,2,2-trifluoro- ethyl, chloromethyl, trichloromethyl, and bromomethyl.
Examples of the C3-C7 cycloalkyl represented by R13 include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
Examples of the Cj-Cζ alkyl represented by R14 and R15 include methyl, ethyl, propyl, butyl, and isopropyl.
Examples of the -C6 haloalkyl represented by R14 and R15 include trifluoromethyl, 2,2,2-trifluoroethyl, 2-chloroethyl, chloromethyl, and trichloromethyl.
Examples of the phenyl optionally substituted by methyl or nitro, which is represented by R14 and R15, include phenyl, p-methylphenyl, 2-nitrophenyl, 3-nitro- phenyl, and 4-nitrophenyl.
Examples of the C\-Cβ alkyl represented by R1 6 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, t-butyl, isoamyl, and t-amyl.
Examples of the haloalkyl represented by R16 include chloromethyl, dichloromethyl, bromomethyl, dibromomethyl, 1-chloroethyl, 1,1-dichloroethyl, 1-bromoethyl, and 1 ,1-dibromoethyl.
Examples of the C2-C6 alkenyl represented by R16 include vinyl, allyl, 1-propenyl, and l -methyl-2-propenyl.
Examples of the C2-C6 haloalkenyl represented by R16 include 3,3-dichloro- 2-propenyl and 3,3-dibromo-2-propenyl.
Examples of the C2-C6 alkynyl represented by R16 include 2-butynyl.
Examples of the C2-C6 haloalkynyl represented by R16 include 3-bromo-2- propynyl.
Examples of the C2-C8 alkoxyalkyl represented by R16 include methoxy- methyl, ethoxymethyl, and isopropoxymethyl.
Examples of the hydroxy Cj-Cό alkyl represented by R16 include hydroxy- methyl.
Examples of the C]-C6 alkyl represented by R17 and R18 include methyl.
Examples of the C1-C3 alkyl represented by R4 include methyl.
Examples of the C\-C , alkyl represented by R5 include methyl, ethyl, propyl, butyl, amyl, isopropyl, isobutyl, and isoamyl.
Examples of the C--C6 haloalkyl represented by R5 include 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and bromodifluoromethyl.
Examples of the C3-C6 alkenyl represented by R5 include allyl, l-methyl-2- propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl.
Examples of the C3-C6 haloalkenyl represented by R5 include 2-chloro-2- propenyl and 3,3-dichloro-2-propenyl.
Examples of the C3-C6 alkynyl represented by R5 include propargyl, l-methyl-2-propynyl, 2-butynyl, and l,l-dimethyl-2-propynyl.
Examples of the C3-C6 haloalkynyl represented by R5 include 3-iodo-2- propynyl and 3-bromo-2-propynyl.
Examples of the cyano -C6 alkyl represented by R5 include cyanomethyl.
Examples of the C2-C8 alkoxyalkyl represented by R5 include methoxy- methyl, ethoxymethyl, and 1-methoxyethyl.
Examples of the C3-C8 alkoxyalkoxyalkyl represented by R5 include methoxyethoxymethyl.
Examples of the carboxy C1-C6 alkyl represented by R5 include carboxy- methyl, 1 -carboxyethyl, and 2-carboxyethyl.
Examples of the (Cj-Cg alkoxy)carbonyl C\-C alkyl represented by R5 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopro¬ poxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycar- bonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonyl- methyl, 1 -methoxycarbonylethyl, 1 -ethoxycarbonylethyl, l-propoxycarbonylethyl, 1-iso- propoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1 -t-butoxycar- bonylethyl, 1 -amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-amyloxycar- bonylethyl.
Examples of the { (C1 -C4 alkoxy) C1-C4 alkoxy} carbonyl alkyl represented by R5 include methoxymethoxycarbonylmethyl and 1 -methoxymethoxy- carbonylethyl.
Examples of the (C3-C8 cycloalkoxy)carbonyl C\-C alkyl represented by R5 include cyclobutyloxycarbonylmethyl, cyclopentyloxycarbonylmethyl, cyclohexyloxy- carbonylmethyl, 1 -cyclobutyloxycarbonylethyl, 1 -cyclopentyloxycarbonylethyl, and 1 -cyclohexyloxycarbonylethyl.
Examples of the C2-C8 alkylthioalkyl represented by R5 include methylthio- methyl.
Examples of the C\-C(, alkylsulfonyl represented by R5 include methane- sulfonyl, ethanesulfonyl, and isopropylsulfonyl.
Examples of the Cj-Cό haloalkylsulfonyl represented by R5 include trifluoro- methanesulfonyl, chloromethanesulfonyl, trichloromethanesulfonyl, 2-chloroethane- sulfonyl, and 2,2,2-trifluoroethanesulfonyl.
Examples of the (Cj -Cs alkyl)carbonyl represented by R5 include acetyl, ethylcarbonyl, propylcarbonyl, and isopropylcarbonyl.
Examples of the (Ci-Cs alkoxy)carbonyl represented by R5 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl, isoamyloxycarbonyl, and t-amyl- oxycarbonyl.
Examples of the hydroxy Ci-Cβ alkyl represented by R5 include hydroxy- methyl, hydroxyethyl, and hydroxypropyl.
Examples of the Cj-Cβ alkyl represented by R6 include methyl and ethyl.
Examples of the C--C6 haloalkyl represented by R6 include bromomethyl, dibromomethyl, tribromomethyl, 1-bromoethyl, chloromethyl, dichloromethyl, and trichloromethyl.
Examples of the hydroxy C--C6 alkyl represented by R6 include hydroxy- methyl.
Examples of the C 1-C6 alkoxy Cj-Cβ alkyl represented by R6 include methoxymethyl, ethoxymethyl, propoxymethyl, and is opropoxy methyl.
Examples of the -C6 alkoxy Cj-Cό alkoxy C\-CQ alkyl represented by R6 include methoxymethoxymethyl, methoxyethoxymethyl, and ethoxymethoxy methyl.
Examples of the alkyl represented by R6 include acetyloxymethyl, ethylcarbonyloxymethyl, and isopropylcarbonyloxymethyl.
Examples of the (C1-C6 haloalkyl)carbonyloxy C--C6 alkyl represented by R 6 include trifluoroacetyloxymethyl, chloroacetyloxymethyl, and trichloroacetyloxy- methyl.
Examples of the (C--C6 alkoxy)carbonyl represented by R6 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, and isoamyloxycarbonyl.
Examples of the (Ci-Cβ alkyl)carbonyl represented by R6 include methyl- carbonyl, ethylcarbonyl, and isopropylcarbonyl.
Examples of the alkyl represented by R7 include methyl.
Examples of the Cj-C6 alkyl represented by R8 include methyl and ethyl.
Examples of the Cj-Cό haloalkyl represented by R8 include chloromethyl, bromomethyl, and fluoro methyl.
Examples of the Cj-Cό hydroxyalkyl represented by R8 include hydroxy- methyl.
Examples of the C2-C8 alkoxyalkyl represented by R8 include methoxy- methyl, ethoxymethyl, isopropoxymethyl, butoxymethyl, and isobutoxymethyl.
Examples of the C3-C10 alkoxyalkoxyalkyl represented by R 8 include methoxymethoxy methyl, methoxyethoxymethyl, and ethoxymethoxymethyl.
Examples of the (C1-C5 alkyl)carbonyloxy -C6 alkyl represented by R8 include acetyloxymethyl, ethylcarbonyloxymethyl, and isopropylcarbonyloxymethyl.
Examples of the Ci-Cξ, haloalkyl)carbonyloxy alkyl represented by R8 include chloromethylcarbonyloxymethyl.
Examples of the carboxy alkyl represented by R8 include carboxy- methyl.
Examples of the (Cι-C8)alkoxycarbonyl represented by R8 include methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, amyloxycarbonyl, isopro- poxycarbonyl, isobutoxycarbonyl, and isoamyloxycarbonyl.
Examples of the (Cj-C6 haloalkoxy)carbonyl represented by R8 include 2-chloroethoxycarbonyl, 2-bromoethoxycarbonyl, 3-chlorobutoxycarbonyl, l-chloro-2- propoxycarbonyl, l,3-dichloro-2-propoxycarbonyl, 2,2-dichloroethoxycarbonyl, 2,2,2- trifluoroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, and 2,2,2-tribromoethoxy- carbonyl.
Examples of the (C3-C10 cycloalkoxy)carbonyl represented by R8 include cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, and cyclohexyloxycarbonyl.
Examples of the (C3-C8 alkenyloxy)carbonyl represented by R8 include allyloxycarbonyl and 3-butenyloxycarbonyl.
Examples of the (C3-C8 alkynyloxy)carbonyl represented by R8 include propargyloxycarbonyl, 3-butynyloxycarbonyl, and l-methyl-2-propynyloxycarbonyl.
Examples of the (C]-C6 alkyl)aminocarbonyl represented by R8 include methylaminocarbonyl, ethylaminocarbonyl, and propylaminocarbonyl.
Examples of the di(C]-C6 alkyl)aminocarbonyl represented by R8 include dimethylaminocarbonyl, diethylaminocarbonyl, and diisopropylaminocarbonyl.
Examples of the (Cι-C6 alkyl)aminocarbonyloxy Cj-Cό alkyl represented by R8 include methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, and propyl- aminocarbonyloxy methyl.
Examples of the di(Cι-C6 alkyl)aminocarbonyloxy Cj-C6 alkyl represented by R8 include dimethylaminocarbonyloxyalkyl and diethylaminocarbonyloxyalkyl.
In the present compounds, preferred substituents from the viewpoint of their herbicidal activity are as follows:
R1 is preferably hydrogen;
R2 is preferably C1-C3 alkyl substituted with one or more halogen atoms, more preferably methyl substituted with one or more fluorine atoms, or ethyl substituted with one or more fluorine atoms, and most preferably trifluoromethyl;
R3 is preferably methyl or ethyl, more preferably methyl;
Q is preferably [Q-l], [Q-2], [Q-3], or [Q-4];
Y is preferably halogen;
Z1 is preferably oxygen or sulfur;
Z2 is preferably oxygen;
B is preferably hydrogen, nitro, -OR 1 0, -SR 1 0, -NHR10, -NHSO2R14, -COOR13, or -CH2CHWCOOR13. wherein W is preferably hydrogen or chlorine; R10 is preferably C \-C(, alkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, cyano -C6 alkyl, or ( -C6 alkoxy)carbonyl C1-C6 alkyl; R13 is preferably C1-C6 alkyl; and R14 is preferably C1-C6 alkyl;
R5 is preferably Cj-C6 alkyl, C3-C6 alkenyl, or C3-C6 alkynyl;
R 6 is preferably Cj-Cό alkyl, Cj -Cό haloalkyl, formyl, hydroxymethyl, C]-C6 alkoxymethyl, C1-C6 alkylcarbonyloxymethyl, or C]-C6 alkoxycarbonyl;
R7 is preferably hydrogen or methyl; and R8 is preferably methyl, hydroxymethyl, CJ-CO alkoxymethyl, (C1-C5 alkyl)- carbonyloxymethyl, carboxyl, or (C]-C6 alkoxy)carbonyl.
Preferred examples of the present compounds from the viewpoint of their herbicidal activity are those which contain the above preferred substituents in combina¬ tion. Among these compounds are more preferred ones wherein R2 is methyl substituted with one or more fluorine atoms, or ethyl substituted with one or more fluorine atoms.
Among these compounds are more preferred ones wherein R2 is trifluoro- methyl.
Among these compounds are more preferred ones wherein Q is [Q-l] or [Q-2].
When Q is [Q-l], more preferred compounds are those wherein B is -OR10 or -NHR 1 0. Among these compounds are more preferred ones wherein when B is -OR10, then R10 is C3-C6 alkynyl or (Ci-Cβ alkoxy)carbonyl C--C6 alkyl; or when B is -NHR10, then R10 is alkyl. Among these compounds are more preferred ones wherein R 10 is C3-C4 alkynyl, (Cj-Cg alkoxy)carbonylmethyl, or 1-(C* -C6 alkoxy)carbonylethyl. Among these compounds are more preferred ones wherein R1 is hydrogen; R3 is methyl; X is fluorine; and Y is chlorine.
When Q is [Q-2], more preferred compounds are those wherein Z1 is oxygen; n is 1 ; R4 is hydrogen; and R5 is C3-C6 alkynyl. Among these compounds are more preferred ones wherein R5 is C3-C4 alkynyl. Among these compounds are those more preferred ones wherein R1 is hydrogen; R3 is methyl; and X is fluorine.
Particularly preferred compounds are those wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-l]; X is fluorine; Y is chlorine; and B is propargyloxy; those wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-l]: X is fluorine; Y is chlorine: and B is l-(ethoxycarbonyl)ethoxy; those wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q- l]; X is fluorine; Y is chlorine; and B is l-(methoxycarbonyl)ethoxy; and those wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-2]; X is fluorine; Z1 is oxygen; n is 1 ; R4 is hydrogen; and R5 is propargyl.
Some of the present compounds have optical isomers based on the presence of at least one asymmetric carbon atom, and all of the optical isomers are, of course, included within the scope of the present invention.
The present compounds can be produced by various production processes as described below.
(Production Process 1)
wherein R1, R2, R3, Q, and D are as defined above.
The reaction is usually effected in the presence of a base in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 100°C. The reaction time is usually in the range of a moment to 96 hours. The amounts of the reagents to be used in the reaction are usually 1 to 5 moles of compound [3] and usually 1 mole to an excess of the base, per mole of compound [2],
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethyl- formamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropyl- ethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; sulfur compounds such as dimethylsulfoxide and sulforane; alcohols such as methanol, ethanol, ethylene glycol, and isopropanol; ketones such as acetone and methyl isobutyl ketone; and mixtures thereof. Examples of the base used in the reaction include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- efhylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato- graphy or recrystallization. Thus the desired compound of the present invention can be isolated.
In the present production process, depending upon the reaction conditions, a compound of the formula:
wherein Q, R1, R2, and R3 are as defined above, may be formed as a by-product and can be isolated in the same manner as in the isolation of the above present compound. Some of the compounds [7] have herbicidal activity.
(Production Process 2)
This is the production process according to the following scheme:
[ 1 - 1 ] [ 1 - 2 ]
[1-3] [1-4]
[ 1-5]
wherein R22 is C--C6 alkyl; R51 is a substituent other than hydrogen, which is included in the definition of R5; and R1, R2, R3, R4, and X are as defined above.
Process for Producing Compound fl-21 from Compound IT-ll
Compound [1-2] can be produced by reacting compound [1-1] with a nitrating agent in a solvent.
Nitrating agent: nitric acid or the like
Amount of nitrating agent: 1 to 10 moles per mole of compound [1-1]
Solvent: sulfuric acid or the like
Temperature: -10°C to room temperature
Time: a moment to 24 hours
Process for Producing Compound [1-31 from Compound Tl-21
Compound [1-3] can be produced by reacting compound [1-2] with a compound of the formula:
R4 HO COOR"
wherein R4 and R22 are as defined above, in the presence of potassium fluoride in a solvent. Amount of compound [8]: 1 to 50 moles per mole of compound [1-2]
Amount of potassium fluoride: 1 to 50 moles per mole of compound [ 1 -2]
Solvent: 1 ,4-dioxane or the like
Temperature: room temperature to refluxing temperature under heating
Time: a moment to 96 hours
Process for Producing Compound [1-41 from Compound H-31
Compound [1-4] can be produced by reducing compound [1-3] with iron powder in the presence of an acid in a solvent.
Amount of iron powder: 3 moles to an excess per mole of compound [1-3]
Acid: acetic acid or the like
Amount of acid: 1 to 10 moles
Solvent: water, ethyl acetate, or the like
Temperature: room temperature to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound [1 -51 from Compound f l-4]
Compound [ 1-5] can be produced by reacting compound [1 -4] with a compound of the formula:
R51-D [9]
wherein R51 and D are as defined above.
The reaction is usually effected in the presence of a base in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 48 hours.
The amounts of the reagents to be used in the reaction are usually 1 to 3 moles of compound [9] and usually 1 to 5 moles of the base, per mole of compound [1 -4].
Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro- benzene and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitro¬ benzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethyl- amine, N,N-diethylaniline, and N-methylmorpholine; ketones such as acetone and methyl isobutyl ketone; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as column chromatography or recrystallization. Thus the present compound [1-5] can be obtained.
The above compound [ 1 -3] can also be produced according to the following scheme:
[ 1 - 6 ] [ 1 - 7 ] t
[1-8] [1-3] wherein R1, R2, R3, R4, R22, and X are as defined above.
Process for Producing Compound fl-71 from Compound fl-61
Compound [1-7] can be produced by reacting compound [1-6] with a compound of the formula:
R4 Br-^ OOR22 r10]
wherein R4 and R22 are as defined above, in the presence of a base in a solvent.
Amount of compound [10]: 1 to 2 moles per mole of compound [1-6]
Base: sodium hydride, potassium carbonate, or the like
Amount of base: 1 to 5 moles per mole of compound [1-6]
Solvent: 1,4-dioxane, N,N-dimethylfoιmamide, or the like
Temperature: 0°tol00°C
Time: a moment to 24 hours
Process for Producing Compound [1-31 from Compound [1-71
Compound [1-3] can be produced by reacting compound [1-7] with a nitrating agent in a solvent.
Nitrating agent: nitric acid or the like
Amount of nitrating agent: 1 to 10 moles per mole of compound [1-7]
Solvent: sulfuric acid, acetic acid, or the like
Temperature: -10°C to room temperature
Time: a moment to 24 hours Process for Producing Compound [1-81 from Compound [1-61
Compound [ 1-8] can be produced by reacting compound [1-6] with a nitrating agent in a solvent.
Nitrating agent: nitric acid or the like
Amount of nitrating agent: 1 to 10 moles per mole of compound [1-6]
Solvent: sulfuric acid, acetic acid, or the like
Temperature: -10°C to room temperature
Time: a moment to 24 hours
Process for Producing Compound [1-31 from Compound [1-81
Compound [1-3] can be produced by reacting compound [1-8] with compound [10] in the presence of a base in a solvent.
Amount of compound [10]: 1 to 2 moles per mole of compound [1-8]
Base: sodium hydride, potassium carbonate, or the like
Amount of base: 1 to 5 moles per mole of compound [1-8]
Solvent: 1,4-dioxane, N,N-dimethylformamide, or the like
Temperature: 0° to 100°C
Time: a moment to 24 hours
(Production Process 3)
This is the production process according to the following scheme:
[ 1 - 9 ]
[ 1 - 1 1 ]
[ 1 - 13 ]
wherein X, R1, R2, R3, R51, and D are as defined above.
Process for Producing Compound [1-101 from Compound [1-91
Compound [1-10] can be produced by reducing compound [1-9] with iron powder in the presence of an acid in a solvent.
Amount of iron powder: 3 moles to an excess per mole of compound [1-9]
Acid: acetic acid or the like
Amount of acid: 1 to 10 moles per mole of compound [1-9]
Solvent: water, ethyl acetate, or the like
Temperature: room temperature to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound [1-11] from Compound IT -101
Compound [1-1 1] can be produced by reacting compound [1 -10] with sodium thiocyanate, potassium thiocyanate, or the like in a solvent, and then reacting it with bromine or chlorine in a solvent.
Amount of sodium thiocyanate, potassium thiocyanate, or the like: 1 to 10 moles per mole of compound [1-10]
Amount of bromine or chlorine: 1 to 10 moles per mole of compound [1-10]
Solvent: aqueous hydrochloric acid, aqueous acetic acid, aqueous sulfuric acid, or the like
Temperature: 0° to 50°C
Time: a moment to 150 hours
Process for Producing Compound [1 -121 from Compound [1-111
Compound [1-12] can be produced by 1) reacting compound [1-1 1 ] with sodium nitrite, potassium nitrite, or the like in a solvent, and then 2) heating it in an acidic solution.
<Reaction 1)>
Amount of sodium nitrite, potassium nitrite, or the like: 1 to 2 moles per mole of compound [1-11]
Solvent: aqueous hydrochloric acid or aqueous sulfuric acid
Temperature: -10° to 10°C
Time: a moment to 5 hours
<Reaction 2)>
Acidic solution: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: 70°C to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound f l-131 from Compound [1-121
Compound [1- 13] can be produced by reacting compound [1-12] with compound [9] in the presence of a base in a solvent.
Amount of compound [9]: 1 to 3 moles per mole of compound [1-12]
Base: sodium hydride, potassium carbonate, or the like
Amount of base: 1 to 10 moles per mole of compound [1-12]
Solvent: 1,4-dioxane, N,N-dimethylformamide, or the like
Temperature: 0° to 100°C
Time: a moment to 48 hours
(Production Process 4)
This is the production process according to the following scheme:
[ 1 - 14 ] [ 1 - 15 ]
[ 1 - 16 ]
wherein X, R1, R2, R3, and R5 are as defined above.
Process for Producing Compound [1-151 from Compound [1-141
Compound [1-15] can be produced by reducing compound [1-14] with iron powder in the presence of an acid in a solvent.
Amount of iron powder: 3 moles to an excess per mole of compound [1-14]
Acid: acetic acid or the like
Amount of acid: 1 to 10 moles per mole of compound [1-14]
Solvent: water, ethyl acetate, or the like
Temperature: room temperature to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound Tl -161 from Compound [1-151
Compound [1-16] can be produced by 1) reacting compound [1-15] with a nitrite salt in a solvent to form a diazonium salt, and then 2) raising the temperature to cause the cyclization of the diazonium salt in a solvent.
<Reaction 1)>
Nitrite salt: sodium nitrite, potassium nitrite, or the like
Amount of nitrite salt: 1 to 2 moles per mole of compound [1-15]
Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: -10° to 10°C
Time: a moment to 5 hours
<Reaction 2)>
Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: room temperature to 80°C Time: a moment to 24 hours
(Production Process 5)
This is the production process according to the following scheme:
[ 1-17] [1-18]
[1-19] [1-20]
[1-21 ]
wherein Y1 is a substituent other than nitro, which is included in the definition of Y; R101 is a substituent other than hydrogen, which is included in the definition of R10; and X, R1, R2, and R3 are as defined above.
Process for Producing Compound ri-181 from compound [1-171
Compound [1-18] can be produced by reacting compound [1-17] with a nitrating agent in a solvent.
Nitrating agent: nitric acid or the like
Amount of nitrating agent: 1 to 10 moles per mole of compound [1-17]
Solvent: sulfuric acid or the like
Temperature: -10°C to room temperature
Time: a moment to 24 hours Process for Producing Compound [1-191 from Compound [1-181
Compound [1-19] can be produced by reducing compound [1-18] with iron powder in the presence of an acid in a solvent.
Amount of iron powder: 3 moles to an excess per mole of compound [1-18]
Acid: acetic acid or the like
Amount of acid: 1 to 10 moles per mole of compound [1-18]
Solvent: water, ethyl acetate, or the like
Temperature: room temperature to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound [1-201 from Compound [1-191
Compound [1-20] can be produced by 1) reacting compound [1-19] with a nitrite salt in a solvent, and then 2) heating it in an acid solution.
<Reaction 1)>
Nitrite salt: sodium nitrite, potassium nitrite, or the like
Amount of nitrite salt: 1 to 2 moles per mole of compound [1-19]
Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: -10° to 10°C
Time: a moment to 5 hours
<Reaction 2)>
Acidic solution: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: 70°C to refluxing temperature under heating
Time: a moment to 24 hours
Process for Producing Compound [1 -211 from Compound [1-201
Compound [1 -21] can be produced by reacting compound [1-20] with a compound of the formula:
R101-D [1 1] or (R101)2O [12]
wherein R101 and D are as defined above.
The reaction is usually effected in the presence of a base in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 48 hours.
The amounts of the reagents to be used in the reaction are usually 1 to 3 moles of compound [11] or [12] and usually 1 to 5 moles of the base, per mole of compound [1-20].
Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro- benzene and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitro¬ benzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylefhylamine, N,N-dimethyl- amine, N,N-diethylaniline, and N-methylmorpholine; ketones such as acetone and methyl isobutyl ketone; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as column chromatography or recrystallization. Thus the present compound [1-21] can be obtained. The above compound [1-20] can also be produced by the following process:
[ 1 - 22 ] [ 1 - 20 ]
wherein X, Y1, R1, R2 and R3 are as defined above.
Process for Producing Compound [1-201 from Compound [1-221
Compound [1-20] can be produced by deprotecting compound [1-22] in the presence of hydrogen bromide-acetic acid or sulfuric acid without any solvent or in a solvent
Amount of hydrogen bromide-acetic acid or sulfuric acid: 1 mole to an excess per mole of compound [1-22]
Solvent: sulfuric acid, acetic acid, or the like
Temperature: 10° to 100°C
Time: a moment to 24 hours
(Production Process 6)
This is the production process according to the following scheme:
[ 1 - 19 ] [ 1 - 23 ]
[ 1 - 24 ] wherein R23 and R24 are independently a substituent included in the definition of R1 1 or R12; or -COR13, -SO2R 14, -SO2R15, or -COOR13, wherein R13, R14, and R15 are as defined above; X, Y1, R1, R2, and R3 are as defined above.
Process for Producing compound [1 -231 from Compound [1-191 Compound [1-23] can be produced by reacting compound [1-19] with a compound of the formula:
R23-D [13] or
(R23)2θ [14]
wherein R23 and D are as defined above, in the presence or absence of a base without any solvent or in a solvent.
Amount of compound [13] or [14]: 1 mole to an excess per mole of compound [1- 19]
Base: organic bases such as pyridine and triethylamine; and inorganic bases such as potassium carbonate
Amount of base : 1 to 3 moles per mole of compound [1-19]
Solvent: N,N-dimethylformamide, 1 ,4-dioxane, or the like
Temperature: 0° to 100°C
Time: a moment to 24 hours
Process for Producing compound [1-241 from Compound [ 1-231
Compound [ 1 -24] can be produced by reacting compound [1-23] with a compound of the formula:
R24-D [15] or
(R24)20 [16]
wherein R24 and D are as defined above, in the presence or absence of a base without any solvent or in a solvent.
Amount of compound [15] or [16]: 1 mole to an excess per mole of compound [1-23]
Base: organic bases such as pyridine and triethylamine; and inorganic bases such as potassium carbonate
Amount of base: 1 to 3 moles per mole of compound [ 1 -23]
Solvent: N,N-dimethylformarnide, 1 ,4-dioxane, or the like
Temperature: 0° to l00°C
Time: a moment to 24 hours
(Production Process 7)
This is the production process according to the following scheme:
[ 1 - 19 ] [ 1 - 25 ]
[ I - 26 ] [ 1 - 27 ]
wherein X, Y1 , R1, R2, R3, and R 101 are as defined above.
Process for Producing compound [1 -251 from compound H -191 Compound [1-25] can be produced by 1 ) reacting compound [1-19] with a nitrite salt in a solvent, and then 2) reacting it with potassium xanthate in a solvent. <Reaction 1)>
Nitrite salt: sodium nitrite, potassium nitrite, or the like Amount of nitrite salt: 1 to 2 moles per mole of compound [1-19] Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: -10° to 10°C
Time: a moment to 5 hours
<Reaction 2)>
Amount of potassium xanthate: 1 to 2 moles per mole of compound [1-19]
Solvent: aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: 0° to 100°C
Time: a moment to 24 hours
(see Org. Syn. Coll., Vol. 3, 809 (1955))
Process for Producing Compound [1-261 from Compound [1-25]
Compound [1-26] can be produced by hydrolyzing compound [1-25] in the presence of a base in a solvent.
Base: inorganic bases such as potassium carbonate
Amount of base: 1 to 5 moles per mole of compound [ 1 -25]
Solvent: alcohols such as methanol and ethanol, or the like
Temperature: 0°C to refluxing temperature under heating
Time: a moment to 24 hours
(see Org. Syn. Coll., Vol. 3, 809 ( 1955))
Process for Producing Compound [1 -271 from Compound [1-261
Compound [ 1-27] can be produced by reacting compound [ 1 -26] with compound [ 1 1 ] or [ 12] in the presence of a base in a solvent.
Amount of compound [1 1 ] or [12] : 1 mole to an excess per mole of compound [ 1-26]
Base: inorganic bases such as potassium carbonate; and organic bases such as triethylamine and pyridine
Amount of base: 1 to 3 moles per mole of compound [ 1 -26] Solvent: 1 ,4-dioxane, N,N-dimethylforrnamide, or the like Temperature: 0° to 100°C Time: a moment to 24 hours
Compound [1-26] can also be produced by the method according to the
[1-17] [1-28]
[1-26]
wherein X, Y1, R1, R2, and R3 are as defined above.
Process for Producing Compound I" 1-281 from Compound [1-171 Compound [1-28] can be produced by reacting compound [1-17] with chlorosulfonic acid without any solvent or in a solvent.
Amount of chlorosulfonic acid: 1 mole to an excess per mole of compound
[1-17]
Solvent: sulfuric acid
Temperature: 0° to 70°C
Time: a moment to 24 hours
(see Org. Syn. Coll., Vol. I, 8 (1941))
Process for Producing Compound [1-261 from Compound [1-281
Compound [1-26] can be produced by reducing compound [1-28] in a solvent.
Reducing agent: zinc, tin chloride, or the like
Amount of reducing agent: 3 moles to an excess per mole of compound
[1-28] Solvent: aqueous acetic acid, aqueous hydrochloric acid, aqueous sulfuric acid, or the like
Temperature: room temperature to 100°C
Time: a moment to 24 hours
(see USP 4,709,049, column 9)
(Production Process 8)
This is the production process according to the following scheme:
[1-19] [1-29]
[1-30]
wherein R241 is bromine or iodine; and X, Y1, R1, R2, R3, and R13 are as defined above.
Process for Producing Compound [1-291 from Compound [1-191 Compound [1-29] can be produced by 1) making a diazonium salt from compound [1-19] in a solvent, and then 2) reacting it with potassium iodide or copper
( I ) bromide in a solvent. <Reaction 1)>
Diazotizing agent: sodium nitrite, potassium nitrite, or the like Amount of diazotizing agent: 1 to 2 moles per mole of compound [1-19] Solvent: aqueous hydrogen bromide, aqueous hydrogen chloride, aqueous sulfuric acid, or the like
Temperature; -10° to 10°C Time: a moment to 5 hours
<Reaction 2)>
Amount of potassium iodide or copper ( I ) bromide: 1 mole to an excess per mole of compound [1-19]
Solvent: aqueous hydrogen bromide, water, or the like
Temperature: 0° to 80°C
Time: a moment to 24 hours
(see Org. Syn. Coll., Vol. 2, 604 (1943), and ibid.,Vo\. 1, 136 (1941))
Process for Producing Compound [1-301 from Compound [1-291
Compound [1-30] can be produced by reacting compound [1-29] with a compound of the formula:
R13-OH [17]
wherein R13 is as defined above, in the presence of a transition metal catalyst and a base in a solvent under an atmosphere of carbon monoxide.
Catalyst: PdCl2(PPh3) or the like
Amount of catalyst: catalytic amount to 0.5 mole per mole of compound
[1-29]
Amount of compound [17]: 1 mole to an excess per mole of compound
[1-29]
Base: organic bases such as diethylamine
Amount of base: 1 to 10 moles per mole of compound [ 1 -29]
Solvent: N,N-dimethylformamide or the like
Atmospheric pressure of carbon monoxide: 1 to 150 at
Temperature: 0° to l00°C
Time: a moment to 72 hours
(see Bull. Chem. Soc. Jpn., 48 (7), 2075 (1975)) (Production Process 9)
The production process according to the following scheme:
[ 1 - 31 ]
[ 1 - 32 ] wherein R131 is an substituent other than hydrogen, which is included in the definition of R13; and X, Y1, R1, R2, R3, and R18 are as defined above.
Process for Producing Compound [1 -31] from Compound [1-291
Compound [1-31] can be produced by reacting compound [1-29] with sodium formate or potassium formate in the presence of a transition metal catalyst in a solvent under an atmosphere of carbon monoxide.
Amount of sodium formate or potassium formate: 1 mole to an excess per mole of compound [1-29]
Solvent: N,N-dimethylformamide or the like
Catalyst: PdCl2(PPh3)2 or the like
Amount of catalyst: catalytic amount to 0.5 mole per mole of compound
[1-29]
Atmospheric pressure of carbon monoxide: 1 atm
Temperature: 0° to 100°C
Time: a moment to 72 hours
(see Bull. Chem. Soc. Jpn., 67, 2329 (1994)) Process for producing compound [1-321 from compound [1-31] Compound [ 1-32] can be produced by reacting compound [1-31] with a compound of the formula:
(C6H5)3P-=CR18COOR131 [18] or
(C2H5O)2P(O)CHR18COOR131 [19]
wherein R18 and R131 are as defined above, in a solvent, and if compound [19] is used, in the presence of a base.
Amount of compound [ 18] or [ 19] : 1 to 5 moles per mole of compound
[1-31]
Solvent: tetrahydrofuran, toluene, or the like
Base: sodium hydride or the like
Amount of base: 1 to 5 moles per mole of compound [1-31]
Temperature: 0° to 50°C
Time: a moment to 24 hours
(Production Process 10)
This is the production process according to the following scheme:
[ 1 - 31 ] [ 1 - 33 ]
[ 1-34] [1-35]
wherein R171 is C]-C6 alkyl; and X, Y1, R1, R2, R3, R18, and R131 are as defined above.
Process for Producing Compound [1-331 from compound [1-311 Compound [1-33] can be produced by reacting compound [1-31] with a compound of the formula:
R171-MgBr [20] or
R171-Li [21]
wherein R171 is as defined above, in a solvent.
Amount of compound [20] or [21]: 1 to 2 moles per mole of compound
[1-31]
Solvent: ether solvents such as tetrahydrofuran
Temperature: -78°C to room temperature
Time: a moment to 24 hours
Process for Producing Compound [1-341 from Compound [1-331
Compound [1-34] can be produced by subjecting compound [1-33] to oxida- tive treatment using chromium (VI) oxide-sulfuric acid, pyridinium chlorochromate, or the like; oxidation using dimethylsulfoxide-acetic anhydride; or Swern oxidation.
Process for producing compound [1-351 from compound [1-341
Compound [1-35] can be produced by reacting compound [1-34] with a compound of the formula: (C6H5)3P=CR18COOR131 [18] or
(C2H5O)2P(O)CHR18COOR131 [19]
wherein R18 and R131 are as defined above, in a solvent, and if compound [19] is used, in the presence of a base.
Amount of compound [18] or [19]: 1 to 5 moles per mole of compound
[1-34]
Solvent: tetrahydrofuran, toluene, or the like
Base: sodium hydride or the like
Amount of base: 1 to 5 moles per mole of compound [ 1 -34]
Temperature: 0° to 50°C
Time: a moment to 24 hours
(Production Process 1 1)
This is the production process according to the following scheme:
[ 1 - 19 ] [ 1 - 36 ]
wherein W2 is chlorine or bromine; and X, Y 1, R 1 , R2, R3, and R13 are as defined above.
Compound [1-36] can be produced by reacting compound [1-19] with t-butyl nitrite or t-amyl nitrite; a compound of the formula:
CuW2 2 [22]
wherein W2 is as defined above; and a compound of the formula: CH2=CHCOOR13 [23]
wherein R13 is as defined above, in a solvent.
Amount of t-butyl nitrite or t-amyl nitrite: 1 to 2 moles per mole of compound [1-19]
Amount of compound [22]: 1 to 2 moles per mole of compound [1-19]
Amount of compound [23]: 10 moles to an excess per mole of compound [1-19]
Solvent: acetonitrile or the like
Temperature: 0° to 50°C
Time: a moment to 24 hours
(see EP 0 649 596, page 11)
(Production Process 12)
This is the production process according to the following scheme:
[ 1 - 28 ] [ 1 - 37 ]
wherein X, Y1, R1, R2, R3, and R10 are as defined above.
Compound [1-37] can be produced by reacting compound [1-28] with a compound of the formula:
R10-OH [24]
wherein R10 is as defined above, in the presence of a base without any solvent or in a solvent.
Amount of compound [24]: 1 mole to an excess per mole of compound [ 1-28] Base: organic bases such as triethylamine; and inorganic bases such as potassium carbonate
Amount of base: 1 to 3 moles per mole of compound [ 1 -28]
Solvent: N,N-dimethylformamide, 1 ,4-dioxane, or the like
Temperature: 0° to l00°C
Time: a moment to 24 hours
(Production Process 13)
This is the production process according to the following scheme:
[ 1 - 28 ] [ 1 - 38 ]
wherein X, Y1, R1, R2, R3, R1 1, and R12 are as defined above.
Compound [1 -38] can be produced by reacting compound [1-28] with a compound of the formula:
Rn(R12)NH [25]
wherein R1 ' and R12 are as defined above, in the presence or absence of a base without any solvent or in a solvent.
Amount of compound [25]: 1 mole to an excess per mole of compound [1-28]
Base: organic bases such as triethylamine; and inorganic bases such as potassium carbonate
Amount of base: 1 to 3 moles per mole of compound [ 1 -28]
Solvent: N,N-dimethylformamide, 1 ,4-dioxane, or the like
Temperature: 0° to l00°C Time: a moment to 24 hours
(Production Process 14)
This is the production process according to the following scheme:
[ 1 - 39 ]
wherein R61 is a substituent other than methyl, which is included in the definition of R6; and X, Y, R1, R2, and R3 are as defined above.
Process for Producing Compound [1-401 from compound π -391
Compound [1-40] can be produced by reacting compound [1-39] with 2,3-dichloropropene in the presence of a base in a solvent.
Amount of 2,3-dichloropropene: 1 to 3 moles per mole of compound [1-39]
Base: inorganic bases such as potassium carbonate
Amount of base: 1 to 5 moles per mole of compound [ 1 -39]
Solvent: N,N-dimethylformamide or the like
Temperature: 0° to l00°C
Time: a moment to 24 hours
Process for Producing Compound [ 1-411 from Compound [1-401
Compound [1-41] can be produced by heating compound [1-40] in a solvent.
Solvent: N,N-dimethylformamide, N,N-dimethylaniline, N,N-diethyl- aniline, m-diisopropylbenzene, or the like Temperature: 70° to 200°C
Time: a moment to 24 hours
Process for Producing Compound [1-421 from Compound [1-411
Compound [1-42] can be produced from compound [1-41] according to the method in which the methyl group in position 2 on the benzofuran ring is replaced with another substituent, as described in USP 5,308,829, columns 2-11.
(Production Process 15)
This is the production process according to the following scheme:
[ 1 - 39 ] [ 1 -43 ]
wherein X, Y, R1, R2, R3, and R7 are as defined above.
Process for Producing Compound [1 -431 from compound [1-391 Compound [1-43] can be produced by reacting compound [1-39] with a compound of the formula:
CH2=CR7CH2W2 [26]
wherein W-" and R7 are as defined above, in the presence of a base in a solvent.
Amount of compound [26]: 1 to 5 moles per mole of compound [1-39] Base: inorganic bases such as potassium carbonate Amount of base: 1 to 5 moles per mole of compound [1-39]
Solvent: N,N-dimethylformamide, 1 ,4-dioxane, or the like
Temperature: 0° to 100°C
Time: a moment to 24 hours
Process for Producing Compound [1-441 from Compound T 1-431
Compound [1-44] can be produced by heating compound [1-43] in a solvent.
Solvent: N,N-dimethylaniline, N,N-diethylaniline, m-diisopropylbenzene, or the like
Temperature: 100° to 200°C
Time: a moment to 24 hours
Process for Producing Compound [1-451 from Compound [1-441
Compound [1-45] can be produced by heating compound [1-44] in the presence of an acid in a solvent.
Acid: organic acids such as p-toluenesulfonic acid; and inorganic acids such as sulfuric acid
Amount of acid: catalytic amount to 1 mole per mole of compound [1-44]
Solvent: toluene, xylene, or the like
Temperature: 100° to 250°C
Time: a moment to 24 hours
(Production Process 16)
This is the production process according to the following scheme:
wherein R81 is a substituent other than methyl and hydroxy methyl, which is included in the definition of R8; and X, Y, R1, R2, R3, and R7 are as defined above.
Process for Producing Compound [1 -46] from Compound [1-441 Compound [1-46] can be produced by reacting compound [1-44] with a peracid in a solvent.
Peracid: m-chloroperbenzoic acid, peracetic acid, or the like Amount of peracid: 1 mole to an excess per mole of compound [1-44] Solvent: halogenated hydrocarbons such as dichloromethane; or organic acids such as acetic acid
Temperature: -20°C to room temperature
Time: a moment to 24 hours
Process for Producing Compound [1-471 from Compound [1-461
Compound [ 1-47] can be produced by reacting compound [1-46] in the presence of a base in a solvent.
Base: potassium carbonate or the like
Amount of base: 1 to 2 moles per mole of compound [ 1 -46]
Solvent: methanol, ethanol, or the like Temperature: 0° to 50°C
Time: a moment to 5 hours
Process for Producing Compound H-481 from Compound [1-471
Compound [1 -48] can be produced from compound [1-47] according to the method in which the hydroxyalkyl group in position 2 on the dihydrobenzofuran ring is replaced with another substituent, as described in USP 5,411,935, columns 5-10.
Compound [2], which is an intermediate compound for the production of the present compounds, can be produced with high efficiency by reacting compound [5] with compound [6] (hereinafter referred to as intermediate production process 1).
The reaction is effected without any solvent or in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 240 hours.
The amounts of the reagents to be used in the reaction, although the propor¬ tion of 1 mole of compound [6] to 1 mole of compound [5] is ideal, can be freely changed depending upon the reaction conditions.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro¬ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-di- ethylaniline, and N-methylmorpholine; sulfur compounds such as dimethylsulfoxide and sulforane; alcohols such as methanol, ethanol, ethylene glycol, and isopropanol; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, or purified by a technique such as column chromatography or recrystallization. Thus the desired compound can be isolated.
In the intermediate production process 1, compound [6] can be replaced with a salt of compound [6] with an organic or inorganic acid (e.g., acetamidine hydrochlo- ride). The reaction is usually effected in the presence of a base in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 240 hours.
The amounts of the compounds to be used in the reaction, although the proportion of 1 mole of compound [6] to 1 mole of compound [5] is ideal, can be freely changed depending upon the reaction conditions. The amount of the base is usually 1 mole to a large excess per mole of the salt of compound [6].
Examples of the base which can be used include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropyl- ethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, and N,N-diethyl- aniline.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro¬ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-di- ethylaniline, and N-methylmorpholine; sulfur compounds such as dimethylsulfoxide and sulforane; alcohols such as methanol, ethanol, ethylene glycol, and isopropanol; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato¬ graphy or recrystallization. Thus the desired compound can be isolated.
Compound [2] can also be produced by reacting a compound of the formula:
wherein Q, R1, and R19 are as defined above, with compound [6] (hereinafter referred to as intermediate production process 2).
The reaction is effected without any solvent or in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 48 hours.
The amounts of the reagents to be used in the reaction, although the propor¬ tion of 1 mole of compound [6] to 1 mole of compound [27] is ideal, can be freely changed depending upon the reaction conditions.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro¬ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as formamide, N,N-dimethylfoπnamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-di- ethylaniline, and N-methylmorpholine; sulfur compounds such as dimefhylsulfoxide and sulforane; alcohols such as methanol, ethanol, ethylene glycol, and isopropanol; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water, if necessary, and subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, or under certain circumstances, the reaction mixture is purified by a technique such as chromatography or recrystallization. Thus the desired compound can be isolated.
In the intermediate production process 2, compound [6] can be replaced with a salt of compound [6] with an organic or inorganic acid (e.g., acetamidine hydrochlo- ride). The reaction is usually effected in the presence of a base in a solvent. The reaction temperature is usually in the range of -20° to 150°C, preferably 0° to 50°C. The reaction time is usually in the range of a moment to 72 hours.
The amounts of the compounds to be used in the reaction, although the proportion of 1 mole of compound [6] to 1 mole of compound [27] is ideal, can be freely changed depending upon the reaction conditions. The amount of the base is usually 1 mole to a large excess per mole of the salt of compound [6].
Examples of the base which can be used include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; and organic bases such as triethylamine, diisopropylethylamine, pyridine, 4-dimethyl- aminopyridine, N,N-dimethylaniline, and N,N-diethylaniline.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chloro¬ form, carbon tetrachloride, dichloromethane, dichloroethane, chlorobenzene, and dichlo- robenzene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; nitro compounds such as nitromethane and nitrobenzene; acid amides such as foπnamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-di- ethylaniline, and N-methylmorpholine; sulfur compounds such as dimethylsulfoxide and sulforane; alcohols such as methanol, ethanol, ethylene glycol, and isopropanol; and mixtures thereof. After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato¬ graphy or recrystallization. Thus the desired compound can be isolated.
Compound [6] can be obtained from commercial sources or can be produced by the method as described in J. Am. Chem. Soc, 78, 6032 (1956).
Compound [5] can be produced, for example, by any of the following methods 1 to 4.
(Method 1) (For compounds wherein R1 is hydrogen)
In this method, compound [27] wherein R1 is hydrogen is reacted with a compound of the formula:
R20-D [28]
wherein R20 and D are as defined above.
The reaction can be effected in the presence of a base in a solvent. The reaction temperature is usually in the range of 0° to 100°C. The reaction time is usually in the range of a moment to 48 hours.
Examples of the base which can be used include inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, and sodium hydride.
Compound [28] includes methyl iodide, methyl bromide, ethyl iodide, ethyl bromide, and isopropyl iodide.
The amounts of the reagents to be used in the reaction are usually 1 mole to a large excess of the base and usually 1 to 5 moles of compound [28], per mole of compound [27].
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro¬ carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water and the precipitated crystals are collected by filtration, or the reaction mixture is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, followed by, if necessary, subsequent purification by a technique such as chromato¬ graphy or recrystallization. Thus the desired compound can be isolated.
(Method 2) (For compounds wherein R1 is any other than hydrogen) In this method, compound [27] wherein R1 is C1-C3 alkyl is reacted with a compound of the formula:
HC(OR20)3 [29]
wherein R20 is as defined above, in the presence of an acid catalyst (e.g., p-toluene¬ sulfonic acid).
(Method 3)
This is the production process according to the following scheme:
[ 30 ] [ 31 ] [ 32 ] [ 5 ]
wherein Q, R1 , R19, and R20 are as defined above; and G is chlorine, bromine, or iodine.
The reaction conditions in the respective steps are described, for example, in JP-A 61-106538/1986. (Method 4) This is the production process according to the following scheme:
19 R1C(OR2ϋ)3 (OR20), base R -OR20
Q-CH2C00RU ~→~ Q- rr→- Q— (' f 35 ^ COOR19 or acld COOR19
[ 34 ] [ 36 ] [ 5 ]
wherein Q, R1, R19, and R20 are as defined above.
The reaction conditions in the respective steps are described, for example, in JP-A 61-106538/1986.
Compound [27] can be obtained by reacting a compound of the formula:
QCH2COOR19 [34]
wherein Q and R19 are as defined above, with a compound of the formula:
R^OOR22 [37]
wherein R1 and R22 are as defined above, in the presence of an appropriate base.
The reaction is usually effected in a solvent. The reaction temperature is usually in the range of -20° to 150°C. The reaction time is usually in the range of a moment to 72 hours.
The amounts of the compounds to be used in the reaction are usually 1 to 10 moles of compound [37] and usually 1 to 20 moles of the base, per mole of compound [34].
Examples of the base which can be used include inorganic bases such as sodium hydride and potassium hydride.
Examples of the solvent which can be used include aliphatic hydrocarbons such as hexane, heptane, ligroin, cyclohexane, and petroleum ether; aromatic hydro- carbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether; acid amides such as formamide, N,N-dimethylformamide, and acetamide; tertiary amines such as pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, and N-methylmorpholine; and mixtures thereof.
After completion of the reaction, the reaction mixture is poured into water and made acidic by the addition of a mineral acid such as hydrochloric acid or sulfuric acid, followed by ordinary post-treatments such as extraction with an organic solvent and concentration, and if necessary, subsequent purification by a technique such as chromato¬ graphy or recrystallization. Thus the desired product can be isolated.
Compound [34] is commercially available, or when the corresponding phenyl- acetic acid (i.e., QCH2COOH) is commercially available, compound [34] can be produced by esterifying this phenylacetic acid according to the ordinary method. However, when neither compound [34] nor the corresponding phenylacetic acid is commercially available, they can be produced, for example, by the following scheme:
1) NaN02 reduction
Q_NH2 *- Q-CN +- QCHO *- QCH2OH
[ 38 ] 2) CuCN r [ 3_9 ], ( step a _ 2 ) [ 40 ] ( step a - 3 ) A [ 41 ] step a - 1 )
R19OH [ 42 ]
H+ _ in reduction
QCOOR 19
( step a - 4 ) ( step a - 5 )
[ 43 ]
halosenation ccyyaanniizzaattiioonn „„ „„II TT , „,.κ.τ RR1ι9yOH [ 42 ]
*► Q-CH2J — *~ Q-CH2CN *\ π i— QCH2COOR 19
( step a - 6 ) ( step a - 7 ) r „ , , H
^ [ 45 ] ( step a - 8 ) ' 34 ϊ
wherein Q and R19 are as defined above, and J is chlorine or bromine.
Compound [40] can also be produced by the following scheme: l) NaN02 PdCl2(PPh3
Q-NH2 •- Q-I ^→- QCHO
Γ O I 2) KI CO, HCOONa
[ 38 ] [ 46 ] [ 40 ]
( step a - 9 ) ( step a - 10 )
wherein Ph is a phenyl group and Q is as defined above.
(Step a- 1 ) can be conducted according to the method as described in Organic Synthesis Collective Volume, 1, 514 (1941);
(Step a-2), Jikken Kagaku Koza (4th ed.) 21, edited by the Chemical Society of Japan, Maruzen K.K., pp. 89-97;
(Step a-3), Jikken Kagaku Koza (4th ed.) 20, edited by the Chemical Society of Japan, Maruzen K.K., pp. 1-10;
(Step a-4) and (Step a-8), Organic Synthesis Collective Volume, J_, 131 (1941);
(Step a-5), Jikken Kagaku Koza (4th ed.) 20, edited by the Chemical Society of Japan, Maruzen K.K., pp. 10-14;
(Step a-6), Organic Synthesis Collective Volume, 3_, 370 (1955) or Organic Synthesis Collective Volume, 6, 634 (1988);
(Step a-7), Organic Synthesis Collective Volume, I, 107 (1941);
(Step a-9), Organic Synthesis Collective Volume, 2, 351 (1943); and
(Step a- 10), Bull. Chem. Soc. Jpn., 67, 2329 (1994).
Compound [38] is known in, or can be produced according to the method as described in, EP-61741-A; USP 4,670,046, USP 4,770,695, USP 4,709,049, USP 4,640,707, USP 4,720,927, USP 5,169,431 ; and JP-A 63-156787/1988.
Some examples of compound [38] can also be produced according to the
[ 47 ] [ 48 ] [ 49 ] wherein R25 is -COR26 or -COOR13, R26 is hydrogen or C--C6 alkyl, and X and Y1 are as defined above.
The present compounds have excellent herbicidal activity, and some of them exhibit excellent selectivity between crop plants and unfavorable weeds. In particular, the present compounds have herbicidal activity against various unfavorable weeds as recited below, which may cause trouble in the foliar treatment and soil treatment on upland fields. Polygonaceae: wild buckwheat (Polygonum convolvulus), pale smartweed (Polygonum lapathifolium), Pennsylvania smartweed (Polygonum pensylvanicum), ladysthumb (Poly¬ gonum persicaήa), curly dock (Rumex crispus), broadleaf dock (Rumex obtusifolius), Japanese knotweed (Polygonum cuspidatum) Portulacaceae: common purslane (Portulaca oleracea) Caryophyllaceae: common chickweed (Stellaήa media) Chenopodiaceae: common lambsquarters (Chenopodium album), kochia (Kochia scoparia) Amaranthaceae: redroot pigweed (Amaranthus retroflexus), smooth pigweed (Amaranthus hybήdus) Crusiferae: wild radish (Raphanus raphanistrum), wild mustard (Sinapis arvensis), shepherdspurse (Capsella bursa-pastoris) Leguminosae: hemp sesbania (Sesbania exaltata), sicklepod (Cassia obtusifolia), Florida beggarweed (Desmodium tortuosum), white clover (Tήfolium repens) Malvaceae: velvetleaf (Abutilon theophrasti), prickly sida (Sida spinosa) Violaceae: field pansy (Viola arvensis), wild pansy (Viola tricolor) Rubiaceae: catchweed bedstraw (cleavers) (Galium aparine) Convolvulaceae: ivyleaf morningglory (Ipomoea hederacea), tall morningglory (Ipomoea purpurea), entireleaf morningglory (Ipomoea hederacea var. integriuscula), pitted morn¬ ingglory (Ipomoea lacunosa), field bindweed (Convolvulus arvensis) Labiatae: red deadnettle (Lamium purpureum), henbit (Lamium amplexicaule) Solanaceae: jimsonweed (Datura stramonium), black nightshade (Solanum nigrum) Scrophulariaceae: birdseye speedwell (Veronica persica), ivyleaf speedwell (Veronica hederae- folia) Compositae: common cocklebur (Xanthium pensylvanicum), common sunflower (Helian- thus annuus), scentless chamomile (Matricaria perforata or inodora), corn marigold (Chiysanthemum segetum), pineappleweed (Matricaria matricarioides), common ragweed (Ambrosia artemisiifolia), giant ragweed (Ambrosia trifida), horseweed (Erigeron canadensis), Japanese mugwort (Artemisia princeps), tall goldenrod (Solidago altissima) Boraginaceae: field forget-me-not (Myosotis arvensis) Asclepiadaceae: common milkweed (Asclepias syriaca) Euphorbiaceae: sun spurge (Euphorbia helioscopia), spotted spurge (Euphorbia maculata) Gramineae: bamyardgrass (Echinochloa crus-galli), green foxtail (Setaria viridis), giant foxtail (Setaria faberi), large crabgrass (Digitaria sanguinalis), goosegrass (Eleusine indica), annual bluegrass (Poa annua), blackgrass (Alopecurus myosuroides), wild oat (Avena fatua), johnsongrass (Sorghum halepense), quackgrass (Agropyron repens), downy brome (Bromus tectorum), bermudagrass (Cynodon dactylon), fall panicum (Panicum dichotomiflorum), Texas panicum (Panicum texanum), shattercane (Sorghum vulgare) Commelinaceae: common dayflower (Commelina communis) Equisetaceae: field horsetail (Equisetum arvense) Cyperaceae: rice flatsedge (Cyperus iria), purple nutsedge (Cyperus rotundus), yellow nutsedge (Cyperus esculentus)
Furthermore, some of the present compounds have no problematic phyto- toxicity on main crops such as com (Zea mays), wheat (Triticum aestivum), barley (Hordeum vulgare), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), cotton (Gossypium spp.), sugar beet (Beta vulgaris), peanut (Arachis hypogaea), sunflower (Helianthus annuus) and canola (Brassica napus); garden crops such as flowers and ornamental plants; and vegetable crops.
The present compounds can attain effective control of unfavorable weeds in the no-tillage cultivation of soybean (Glycine max), com (Zea mays), and wheat (Triticum aestivum). Furthermore, some of them exhibit no problematic phytotoxicity on crop plants.
The present compounds have herbicidal activity against various unfavorable weeds as recited below under the flooding treatment on paddy fields. Gramineae: barnyardgrass (Echinochloa oryzicola) Scrophulariaceae: common falsepimpemel (Lindernia procumbens) Lythraceae:
Rotala indica, Ammannia multiflora Elatinaceae:
Elatine triandra Cyperaceae: smallflower umbrellaplant (Cyperus difformis), hardstem bulrush (Scirpus juncoides), needle spikerush (Eleocharis acicularis), Cyperus serotinus, Eleocharis kuroguwai Pontederiaceae:
Monochoria vaginalis Alismataceae:
Sagittaria pygmaea, Sagittaria trifolia, Alisma canaliculatum Potamogetonaceae : roundleaf pondweed (Potamogeton distinctus) Umbelliferae:
Oenanthe javanica
Furthermore, some of the present compounds have no problematic phyto- toxicity on transplanted paddy rice.
The present compounds can attain effective control of various unfavorable weeds in orchards, grasslands, lawns, forests, waterways, canals, or other non- cultivated lands.
The present compounds also have herbicidal activity against various aquatic plants such as water hyacinth (Eichhornia crassipes), which will grow in waterways, canals, or the like.
The present compounds have substantially the same characteristics as those of the herbicidal compounds described in the publication of International Patent Application WO95/34659. In the case where crop plants with tolerance imparted by introducing a herbicide tolerance gene described in the publication are cultivated, the present compounds can be used at greater doses than those used when ordinary crop plants without tolerance are cultivated, and it is, therefore, possible to attain effective control of other unfavorable plants.
When the present compounds are used as active ingredients of herbicides, they are usually mixed with solid or liquid carriers or diluents, surfactants, and other auxiliary agents to give formulations such as emulsifiable concentrates, wettable powders, flowables, granules, concentrated emulsions, and water-dispersible granules.
These formulations may contain any of the present compounds as an active ingredient at an amount of 0.001 % to 80% by weight, preferably 0.005% to 70% by weight, based on the total weight of the formulation.
Examples of the solid carrier or diluent may include fine powders or granules of the following materials: mineral matters such as kaolin clay, attapulgite clay, bentonite, terra alba, pyrophyllite, talc, diatomaceous earth, and calcite; organic substances such as walnut shell powder; water-soluble organic substances such as urea; inorganic salts such as ammonium sulfate; and synthetic hydrated silicon oxide. Examples of the liquid carrier or diluent may include aromatic hydrocarbons such as methylnaphthalene, phenylxylylethane, and alkylbenzenes (e.g., xylene); alcohols such as isopropanol, ethylene glycol, and 2-ethoxyethanol; esters such as phthalic acid dialkyl esters; ketones such as acetone, cyclohexanone, and isophorone; mineral oils such as machine oil; vegetable oils such as soybean oil and cotton seed oil; dimethylsulfoxide, N,N-dimethylformamide, acetonitrile, N-methylpyrrolidone, water, and the like.
Examples of the surfactant used for emulsification, dispersing, or spreading may include surfactants of the anionic type, such as alkylsulfates, alkylsulfonates, alkylarylsulfonates, dialkylsulfosuccinates, and phosphates of polyoxyethylene alkyl aryl ethers; and surfactants of the nonionic type, such as polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters.
Examples of the auxiliary agent used for formulation may include lignin- sulfonates, alginates, polyvinyl alcohol, gum arabic, carboxymethyl cellulose (CMC), and isopropyl acid phosphate (PAP).
The present compounds are usually formulated as described above and then used for the pre- or post-emergence soil, foliar, or flooding treatment of unfavorable weeds. The soil treatment may include soil surface treatment and soil incorporation. The foliar treatment may include application over the plants and directed application in which a chemical is applied only to the unfavorable weeds so as to keep off the crop plants.
The present compounds can be used, if necessary, in combination with other compounds having herbicidal activity. Examples of the compounds which can be used in combination with the present compounds may include various compounds described in Catalog 1995 Edition of Farm Chemicals Handbook (Meister Publishing Company); AG CHEM NEW COMPOUND REVIEW, VOL. 13, 1995 (AG CHEM INFORMATION SERVICE); JOSOUZAI KENKYU SOURAN (Hakuyu-sha); or HERBICIDE HAND¬ BOOK Seven Edition (Weed Science Society of America). Typical examples of such compounds are as follows: atrazin, cyanazine, dimethametryn, metribuzin, prometryn, simazine, simetryn, chlorotoluron, diuron, dymuron, fluometuron, isoproturon, linuron, methabenzthiazuron, bromoxynil, ioxynil, ethalfluralin, pendimethalin, trifluralin, acifluorfen, acifluorfen-sodium, bifenox, chlomethoxynil, fomesafen, lactofen, oxadiazon, oxyfluorfen, carfentrazone, flumiclorac-pentyl, flumioxazine, fluthiacet- methyl, sulfentrazone, thidiazimin, difenzoquat, diquat, paraquat, 2,4-D, 2,4-DB, DCPA, MCPA, MCPB, clomeprop, clopyralid, dicamba, dithiopyr, fluroxypyr, mecoprop, naploanilide, phenothiol, quinclorac, triclopyr, acetochlor, alachlor, butachlor, diethatylethyl, metolachlor, pretilachlor, propachlor, bensulfuron-methyl, chlorsulfuron, chlorimuron-ethyl, halosulfuron-methyl, metsulfuron-methyl, nico- sulfuron, primisulfuron, pyrazosulfuron-ethyl, sulfometuron-methyl, thifensulfuron- methyl, triasulfuron, tribenuron-methyl, azimsulfuron, cloransulam-methyl, cyclo- sulfamuron, flumeturam, flupyrsulfuron, flazasulfuron, imazosulfuron, metosulam, prosulfuron, rimsulfuron, triflusulfuron-methyl, imazamethabenz-methyl, imazapyr, imazaquin, imazethapyr, imazameth, imazamox, bispyribac-sodium, pyriminobac- methyl, pyrithiobac-sodium, alloxydim-sodium, clethodim, sethoxydim, tralkoxydim, diclofop-methyl, fenoxaprop-ethyl, fenoxaprop-p-ethyl, fluazifop-butyl, fluazifop-p- butyl, haloxyfop-methyl, quizalofop-p-ethyl, cyhalofop-butyl, clodinafop-propargyl, benzofenap, clomazone, diflufenican, norflurazon, pyrazolate, pyrazoxyfen, isoxaflutole, sulcotrione, glufosinate-ammonium, glyphosate, bentazon, benthiocarb, bromobutide, butamifos, butylate, dimepiperate, dimethenamid, DSMA, EPTC, esprocarb, isoxaben, mefenacet, molinate, MSMA, piperophos, pributycarb, propanil, pyridate, triallate, cafenstrol, flupoxam, and thiafluamide.
In some cases, the present compounds may be used in combination with other herbicides to enhance their herbicidal activity. Furthermore, the present compounds can also be used in combination with insecticides, acaricides, nematocides, fungicides, plant growth regulators, fertilizers, soil improver, or the like.
When the present compounds are used as active ingredients of herbicides, the application amount is usually in the range of 0.01 to 10,000 g, preferably 1 to 8000 g, per hectare, although it may vary depending upon the weather conditions, formulation type, application timing, application method, soil conditions, crop plants, unfavorable weeds, and the like. In the case of emulsifiable concentrates, wettable powders, flow¬ ables, concentrated emulsions, water-dispersible granules, or the like, the formulation is usually applied at a prescribed amount after diluted with water having a volume of about 10 to 1000 liters per hectare, if necessary, with the addition of an adjuvant such as a spreading agent. In the case of granules or some types of flowables, the formulation is usually applied as such without any dilution.
Examples of the adjuvant used, if necessary, may include, in addition to the surfactants recited above, polyoxyethylene resin acids (esters), ligninsulfonates, abietates, dinaphthylmethanedisulfonates, crop oil concentrates, and vegetable oils such as soybean oil, corn oil, cotton seed oil, and sunflower oil.
The present compounds can also be used as active ingredients of harvesting aids such as defoliants and desiccating agents for cotton, and desiccating agents for potato. In these cases, the present compounds are usually formulated in the same manner as the case where they are used as active ingredients of herbicides, and used alone or in combination with other harvesting aids for foliar treatment before the harvesting of crops.
The present invention will be further illustrated by the following production examples, formulation examples, and test examples; however, the present invention is not limited to these examples.
The following will describe production examples for the present compounds, where the present compounds are designated by their compound numbers shown in Tables 1 to 5 and the intermediate compounds are designated by their compound numbers shown in Tables 6 to 8. For the measurement of 1H-NMR, tetramethylsilane was used as an internal standard.
Production Example 1
( 1) First, 0.5 g of compound 1-1010 was dissolved in 5 ml of N,N-di- methylformamide, to which 0.5 g of potassium carbonate and 0.5 ml of methyl iodide were added, and the mixture was stirred at room temperature for 15 hours. After comple¬ tion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to preparative thin layer chromatography (using hexane-ethyl acetate 9 : 1 as an eluent), which afforded 0.1 g of compound 1-340.
Η-NMR (60 MHz, CDC13): δ (ppm) 3.70 (3H, s), 6.70-7.05 (2H, ), 7.25-7.65 ( 1 H, m), 8.00 (1 H, s)
(2) Then, 0.45 g of compound 1-340 was poured into 10 ml of concen¬ trated sulfuric acid at 0°C, to which 0.3 ml of nitric acid (d = 1.42) was added, and the mixture was stirred at 0° to 5°C for 1 hour. After completion of the reaction, the reaction mixture was added to ice water, and the precipitated crystals were collected by filtration. The crystals were dissolved in ethyl acetate, and the solution was washed with water. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.45 g of compound 1-346.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.76 (3H, s), 7.17 (1H, dd, J = 10.0, 10.0 Hz), 8.16 (1H, d, J = 1.6 Hz), 8.45 (1H, dd, J = 7.3, 7.3 Hz)
(3) Then, 1.2 g of compound 1-346 was dissolved in 10 ml of 1,4-di- oxane, to which 1.0 g of potassium fluoride and 1.0 ml of butyl glycolate were added, and the mixture was heated under reflux for 24 hours. After completion of the reaction, the reaction mixture was allowed to stand for cooling to room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, which afforded 1.2 g of the present compound represented by the following formula:
F CH3CH2CH2CH2OOCCH2O - V-CF3
02N o ^
(4) Then, 2.0 g of iron powder was added to a mixed solution of 3 ml of acetic acid and 30 ml of water, followed by heating to 50°C, to which a solution of 1.2 g of the present compound obtained in the previous step (3) dissolved in 15 ml of ethyl acetate and 15 ml of acetic acid was slowly added dropwise. The mixture was stirred at an internal temperature of 60° to 70°C for 40 minutes. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was subjected to phase separation with ethyl acetate-aqueous sodium hydrogencarbonate solution. The organic layer was washed with water, dried, and concentrated, which afforded 1.0 g of compound 2-239, m.p. 194.0°C.
(5) Then, 1.0 g of compound 2-239 was dissolved in 15 ml of N,N-di- methylformamide, to which 1.6 g of potassium carbonate and 1.0 ml of propargyl bromide were added, and the mixture was stirred at room temperature for l - g hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, followed by recrystallization, which afforded 0.7 g of compound 2-251.
1H-NMR (250 MHz, CDC13): 5 (ppm) 2.27 (1H, t, J = 2.5 Hz), 3.73 (3H, s), 4.68 (2H, s), 4.70 (2H, d, J = 2.5 Hz), 6.86 (1H, d, J = 10.2 Hz), 7.40 (1H, d, J = 6.7 Hz), 8.1 1 (1H, d, J = 1.7 Hz)
Production Example 2
First, 2.0 g of compound 1-1002 was dissolved in 30 ml of N,N-dimethyl- formamide, to which 2.17 g of potassium carbonate and 2.0 ml of methyl iodide were added, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.65 g of compound 1-5. H-NMR (60 MHz, CDCI3): δ (ppm) 2.40 (3H, s), 3.60 (3H, s), 7.35 (2H, d, J = 9 Hz), 7.60 (2H, d, J = 9 Hz), 7.90 (1H, s)
Production Example 3
First, 0.5 g of compound 1-1004 was dissolved in 10 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of methyl iodide were added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.1 g of compound 1-10.
•H-NMR (60 MHz, CDCI3): δ (ppm) 2.55 (3H, s), 3.55 (3H, s), 6.60- 7.00 (2H, m), 7.20-7.50 (1 H, m), 7.85 (1H, s)
Production Example 4
First, 2.0 g of compound 1-1013 was dissolved in 30 ml of N,N-dimethyl- formamide, to which 2.17 g of potassium carbonate and 2.0 ml of methyl iodide were added, and the mixture was stirred at room temperature for 90 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was recrystallized, which afforded 1.16 g of compound 1-662.
!H-NMR (60 MHz, CDC13): δ (ppm) 2.60 (3H, s), 3.60 (3H, s), 7.30 (2H, m), 7.45 (1H, m), 7.85 (1H, s)
Production Example 5
First, 0.3 g of compound 1-1008 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.3 g of potassium carbonate and 0.3 ml of methyl iodide were added, and the mixture was stirred at room temperature for 75 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.1 g of compound 1-335.
1H-NMR (60 MHz, CDCI3): δ (ppm) 3.75 (3H, s), 7.35 (2H, d, J = 9 Hz), 7.60 (2H, d, J = 9 Hz), 8.00 (1H, s)
The structure of compound 1-335 was also confirmed by X-ray crystallo¬ graphy.
Production Example 6
First, 2.0 g of compound 1-1014 was dissolved in 20 ml of N,N-dimethyl- formamide, to which 2.5 g of potassium carbonate and 2.0 ml of methyl iodide were added, and the mixture was stirred at 100°C for 15 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 0.9 g of compound 1 -476.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.38 (6H, d, J = 6.1 Hz), 3.73 (3H, s), 4.50 (1 H, hp, J = 6.1 Hz), 7.20 (1H, d,J = 6.6 Hz), 7.23 (1H, d, J = 9.6 Hz), 8.12 ( 1H, d, J = 1.8 Hz)
Production Example 7
First, 0.7 g of compound 1-476 was poured into 10 ml of concentrated sulfuric acid, and the mixture was stirred at room temperature for 20 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.5 g of compound 1-391.
1H-NMR (300 MHz, CDC13): δ (ppm) 3.73 (3H, s), 5.45 (1H, s), 7.19 ( 1H, d, J = 9.1 Hz), 7.20 (1H, d,J = 6.5 Hz), 8.07 (1H, d, J = 2 Hz)
Production Example 8
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of allyl chloride were added, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0. l l g of compound 1-482.
1H-NMR (300 MHz, CDCI3): δ (ppm) 3.73 (3H, s), 4.60 (2H, d, J = 5.2 Hz), 5.33 (1H, dd, J = 9.5, 1 Hz), 5.45 (1H, dd,J = 16, 1 Hz), 6.06 (1H, tdd, J = 5.2, 16, 9.5 Hz), 7.18 ( 1 H, d, J = 6.4 Hz), 7.24 (1H, d, J = 9.6 Hz), 8.1 1 (1H, d, J = 1.6 Hz)
Production Example 9
First, 0.25 g of compound 1-391 was dissolved in 8 ml of N,N-dimethyl- formamide, to which 0.3 g of potassium carbonate and 0.3 ml of propargyl bromide were added, and the mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel preparative thin layer chromato¬ graphy, which afforded 0.25 g of compound 1-486.
!H-NMR (250 MHz, CDC13): δ (ppm) 2.57 (IH, t, J = 2.5 Hz), 3.74 (3H, s), 4.78 (2H, d, J = 2.5 Hz), 7.26 (IH, d,J = 9.4 Hz), 7.32 (IH, d, J = 6.4 Hz), 8.12 ( IH, d, J = 1.7 Hz)
Production Example 10
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of 3-bromo-l-butyne were added, and the mixture was stirred at room temperature for 45 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.2 g of compound 1-487.
1H-NMR (300 MHz, CDCI3): δ (ppm) 1.72 (3H, d, J = 6.6 Hz), 2.53 (IH, d, J = 1.9 Hz), 3.73 (3H, s), 4.86 (IH, dt, J = 1.9, 6.7 Hz), 7.24 (IH, d, J = 9.4 Hz), 7.39 (IH, d, J = 6.5 Hz), 8.1 1 ( IH, s)
Production Example 1 1
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of methyl bromoacetate were added, and the mixture was stirred at room temperature for 21 hours. After comple¬ tion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.32 g of compound 1-495.
•H-NMR (300 MHz, CDCI3): δ (ppm) 3.72 (3H, s), 3.81 (3H, s), 4.71 (2H, s), 7.18 ( I H, d, J = 6.3 Hz), 7.26 (IH, d, J = 9.4 Hz), 8.1 1 (IH, d, J = 1.8 Hz)
Production Example 12
First, 0.27 g of compound 1-391 was dissolved in 8 ml of N,N-dimethyl- formamide, to which 0.3 g of potassium carbonate and 0.3 ml of ethyl bromoacetate were added, and the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel preparative thin layer chromato¬ graphy, which afforded 0.34 g of compound 1-496.
1H-NMR (300 MHz, CDC13): δ (ppm) 1.30 (3H, t, J = 7.1 Hz), 3.72 (3H, s), 4.27 (2H, q, J = 7.1 Hz), 4.69 (2H, s), 7.19 (IH, d, J = 6.4 Hz), 7.26 (IH, d, J = 9.5 Hz), 8.1 1 (IH, d, J = 1.7 Hz)
Production Example 13
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of n-amyl chloroacetate were added, and the mixture was stirred at room temperature for 24 hours. After comple¬ tion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.18 g of compound 1-499.
1H-NMR (300 MHz, CDCI3): δ (ppm) 0.88 (3H, t, J = 6.8 Hz), 1.25-1.45 (4H, m), 1.55-1.70 (2H, m), 3.72 (3H, s), 4.19 (2H, t, J = 6.7 Hz), 4.70 (2H, s), 7.18 ( IH, d, J = 6.4 Hz), 7.26 (IH, d, J = 9.4 Hz), 8.1 1 (I H, s)
Production Example 14
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of methyl 2-bromo- propionate were added, and the mixture was stirred at room temperature for 23.5 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.25 g of compound 1-503. 1H-NMR (300 MHz, CDC13): δ (ppm) 1.67 (3H, d, J = 6.7 Hz), 3.71 (3H, s), 3.78 (3H, s), 4.74 ( IH, q, J = 6.7 Hz), 7.17 (IH, d, J = 6.4 Hz), 7.24 (IH, d, J =
9.8 Hz), 8.09 (IH, d, J = 1.7 Hz)
Production Example 15
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.5 g of potassium carbonate and 0.5 ml of ethyl 2-bromo- propionate were added, and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solu¬ tion, dried, and concentrated. The residue was subjected to silica gel column chromato¬ graphy, which afforded 0.36 g of compound 1-504.
1H-NMR (300 MHz, CDCI3): δ (ppm) 1.26 (3H, t, J = 7.1 Hz), 1.67 (3H, d, J = 6.7 Hz), 3.71 (3H, s), 4.23 (2H, q, J = 7.1 Hz), 4.73 (IH, q, J = 6.7 Hz), 7.18 ( IH, d, J = 6.4 Hz), 7.24 (IH, d, J = 9.9 Hz), 8.09 (IH, d, J = 2 Hz)
Production Example 16
First, 0.4 g of compound 2-239 was dissolved in 10 ml of N,N-dimethyl- formamide, to which 0.4 g of potassium carbonate and 0.4 ml of 3-bromo-l-butyne were added, and the reaction was allowed to proceed at room temperature for 18.5 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to preparative thin layer chromatography, which afforded 0.11 g of compound 2-252.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.66 (3H, d, J = 7.3 Hz), 2.45 (IH, d, J = 2.6 Hz), 3.74 (3H, br), 4.60 (IH, d, J = 15.2 Hz), 4.67 (IH, d, J = 15.2 Hz),
6.09 ( I H, dq, J = 2.6, 7.3 Hz), 6.87 (IH, d, J = 10.2 Hz), 7.89 ( IH, d, J = 7.0 Hz), 8.12 ( IH, d, J = 1.8 Hz)
Production Example 17
( 1) First, 5.5 g of compound 1-1007 was dissolved in 50 ml of N,N-di- methylformamide, to which 4.0 g of potassium carbonate and 2.5 ml of methyl iodide were added, and the mixture was stirred at room temperature for 4*1/3 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was successively washed with water and saturated sodium chloride solution, dried with magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.16 g of compound 1-334.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.73 (3H, s), 7.15 (2H, dd, J = 8.5, 8.5 Hz), 7.68 (2H, dd, J = 5.4, 8.5 Hz), 8.70 (IH, s)
(2) Then, 1.0 g of compound 1-334 was suspended in 15 ml of sulfuric acid at 0°C, to which 0.5 ml of nitric acid (d = 1.42) was slowly added dropwise with stirring, and the mixture was stirred at 5°C for 1.25 hours. After completion of the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was successively washed with water and saturated sodium chloride solution,* dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 1.0 g of compound 1-343.
JH-NMR (250 MHz, CDCI3): δ (ppm) 3.76 (3H, s), 7.40 (IH, dd, J = 8.7, 10.4 Hz), 8.00 (IH, ddd, J = 2.4, 6.5, 8.7 Hz), 8.17 (IH, s), 8.46 (IH, dd, J = 7.1 , 2.4 Hz)
(3) Then, 1.0 g of compound 1-343 was dissolved in 10 ml of 1 ,4-di¬ oxane, to which 1.0 g of potassium fluoride and 0.7 ml of n-butyl glycolate were added, and the mixture was heated under reflux for 60 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 1.0 g of the present compound represented by the following formula:
(4) Then, 1.5 g of iron powder was added to a mixed solution of 2.0 ml of acetic acid and 20 ml of water, followed by heating to 50°C, to which a solution of 1.0 g of the present compound obtained in the previous step (3) dissolved in 15 ml of ethyl acetate and 15 ml of acetic acid was slowly added dropwise, and the mixture was stirred at an internal temperature of 50°C for 25 minutes. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was subjected to phase separation with ethyl acetate-saturated aqueous sodium hydrogencarbonate solution. The organic layer was successively washed with water and saturated sodium chloride solution, dried, and concentrated. The residue was recrystallized from hexane-ethyl acetate, which afforded 0.6 g of compound 2-191.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.73 (3H, s), 4.66 (2H, s), 7.05 ( IH, d, J = 8.4 Hz), 7.22-7.32 (2H, m), 8.08 (IH, s)
(5) Then, 0.6 g of compound 2-191 was dissolved in 15 ml of N,N-di- methylformamide, to which 0.8 g of potassium carbonate and 0.8 ml of propargyl bromide were added, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.6 g of compound 2-203.
1H-NMR (250 MHz, CDCI3): δ (ppm) 2.29 (IH, t, J = 2.5 Hz), 3.74 (3H, s), 4.69 (2H, s), 4.75 (2H, d, J = 2.5 Hz), 7.09 (IH, d, J = 8.4 Hz), 7.36 (IH, dd, J = 2.0, 8.4 Hz), 7.61 ( I H, d, J = 2.0 Hz), 8.1 1 (IH, s)
Production Example 18
First, 0.3 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.3 g of potassium carbonate and 0.5 ml of chloroacetonitrile were added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to preparative thin layer chromatography, which afforded 0.3 g of compound 1-491.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.74 (3H, s), 4.84 (2H, s), 7.31 (IH, d, J = 9.4 Hz), 7.42 (IH, d, J = 6.3 Hz), 8.16 (IH, d, J = 1.8 Hz)
Production Example 19
First, 2.0 g of iron powder was added to a mixed solution of 5.0 ml of acetic acid and 50 ml of water, followed by heating to 50°C, to which a solution of 3.0 g of compound 1-346 in 30 ml of ethyl acetate and 10 ml of acetic acid was slowly added dropwise, and the mixture was stiπed at an internal temperature of 50° to 60°C for 30 minutes. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was subjected to phase separation with ethyl acetate-saturated aqueous sodium hydrogencarbonate solution. The organic layer was successively washed with water and saturated sodium chloride solution, dried, and concentrated. The precipitated crystals were recrystallized from hexane-ethyl acetate, which afforded 2.4 g of compound 1-352.
1H-NMR (250 MHz, CDCI3): δ (ppm) 3.67 (2H, br), 3.72 (3H, s), 6.89 (IH, dd, J = 9.8, 10.6 Hz), 6.96 (IH, dd, J = 7.1, 9.6 Hz), 8.06 ( IH, d, J = 1.6 Hz)
Production Example 20
First, 0.8 g of compound 1-352 was dissolved in 8 ml of ethyl 2-bromo- propionate, and the mixture was stirred at 80°C for 10 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 0.36 g of compound 1 -663.
Η-NMR (250 MHz, CDCI3): δ (ppm) 1.26 (3H, t, J = 7.0 Hz), 1.50 (3H, d, J = 6.9 Hz), 3.72 (3H, s), 4.04-4.14 (IH, m), 4.20 (2H, q, J = 7.0 Hz), 4.28-4.33 ( IH, m), 6.77 (IH, dd, J = 6.9, 9.4 Hz), 6.90 (IH, dd, J = 9.7, 1 1.0 Hz), 8.04 (IH, d, J = 1.5 Hz)
Production Example 21
First, 9.4 g of compound 1-1015 was dissolved in 100 ml of N,N-dimethyl- formamide, to which 10 g of potassium carbonate and 5.0 ml of methyl iodide were added, and the mixture was stiπed at 100°C for 10 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 1.7 g of compound 1-664.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.73 (3H, s), 7.29 (IH, d, J = 8.2 Hz), 7.34 (IH, dd, J = 1.8, 8.2 Hz), 7.52 (IH, d, J = 1.8 Hz), 8.00 (IH, s)
Production Example 22
First, 1.4 g of compound 1-664 was pulverized with a mortar and poured into 20 ml of sulfuric acid cooled to 5°C, followed by stirring for 10 minutes, to which 1.0 ml of nitric acid (d = 1.42) was slowly added dropwise, and the mixture was further stiπed at 5°C for 1 hour. After completion of the reaction, the reaction mixture was poured into ice water, and the precipitated crystals were collected by filtration. The crystals were dissolved in ethyl acetate, and the solution was washed with water. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated, which afforded 1.4 g of compound 1-665.
1H-NMR (250 MHz, CDCI3): δ (ppm) 3.75 (3H, s), 7.73 (IH, s), 8.00 (I H, s), 8.08 (I H, s)
Production Example 23
First, 3.0 g of iron powder was added to a mixed solution of 3.0 ml of acetic acid and 30 ml of water, followed by heating to 50°C, to which a solution of 1.2 g of compound 1 -665 in 10 ml of ethyl acetate and 10 ml of acetic acid was slowly added dropwise, and the mixture was stiπed at an internal temperature of 70°C for 25 minutes. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was subjected to phase separation with ethyl acetate-saturated aqueous sodium hydrogencarbonate solution. The organic layer was successively washed with water and saturated sodium chloride solution, dried, and concentrated. The residue was recrystal- lized from hexane-ethyl acetate, which afforded 1.0 g of compound 1-666.
1H-NMR (250 MHz, CDC13): δ (ppm) 3.72 (3H, br), 4.12 (2H, br), 6.74 ( IH, s), 7.39 (IH, s), 7.98 (IH, s)
Production Example 24
First, 1.0 g of compound 1-666 was dissolved in 10 ml of ethyl 2-bromo- propionate, and the mixture was stiπed at 80°C for 33 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was successively subjected to silica gel column chromatography and preparative thin layer chromatography, which afforded 0.25 g of compound 1-667.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.26 (3H, t, J = 7.0 Hz), 1.51 (3H, d, J = 6.9 Hz), 3.73 (3H, s), 4.10 ( IH, dq, J = 7.6, 6.9 Hz), 4.21 (2H, d, J = 7.0 Hz), 4.90 (IH, d, J = 7.6 Hz), 6.52 ( IH, s), 7.41 (IH, s), 7.97 (IH, s)
Production Example 25
First, 0.5 g of compound 1-666 was dissolved in 5 ml of pyridine, to which 0.3 ml of methanesulfonyl chloride was added, and the reaction was allowed to proceed at room temperature for 23 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated, after which the pyridine was removed by azeotropic distillation with toluene. The residue was subjected to silica gel column chromatography, which afforded 0.4 g of compound 1-668.
1H-NMR (250 MHz, CDCI3): δ (ppm) 3.08 (3H, s), 3.74 (3H, s), 6.89 ( IH, br), 7.59 ( I H, s), 7.67 ( IH, s), 8.04 (IH, s) Production Example 26
First, 25.6 g of compound 1-101 1 was dissolved in 200 ml of N,N-dimethyl- formamide, to which 40 g of potassium carbonate and 40 ml of methyl iodide were added, and the mixture was stirred at 100°C for 6-2/3 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 7.0 g of compound 1-341.
1H-NMR (300 MHz, CDC13): δ (ppm) 3.73 (3H, s), 7.19-7.26 (2H, m), 7.49 (IH, dd, J = 7.8, 7.8 Hz), 8.08 (IH, d, J = 1.4 Hz)
Production Example 27
First, 7.0 g of compound 1-341 was poured into 100 ml of sulfuric acid at 0°C, to which 3.0 ml of nitric acid (d = 1.42) was slowly added dropwise, and the mixture was stiπed at 0°C for 1 V3 hours. After completion of the reaction, the reaction mixture was poured into water, and the precipitated crystals were collected by filtration. The crystals were dissolved in ethyl acetate, and the solution was washed with water. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The crystals were recrystallized from hexane-ethyl acetate, which afforded 7.6 g of compound 1 -347, m.p. 135.2°C.
Production Example 28
First, 7.7 g of iron powder was added to a mixed solution of 5.0 ml of acetic acid and 50 ml of water, followed by heating to 50°C, to which a solution of 7.7 g of compound 1 -347 in 50 ml of ethyl acetate and 50 ml of acetic acid was slowly added dropwise, and the mixture was stiπed at an internal temperature of 50° to 70°C for 50 minutes. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was subjected to phase separation with ethyl acetate-saturated aqueous sodium hydrogencarbonate solution. The organic layer was successively washed with water and saturated sodium chloride solution, dried, and concentrated. The precipitated crystals were recrystallized from hexane-ethyl acetate, which afforded 6.4 g of compound 1-353, m.p. 152.7°C.
Production Example 29
First, 0.7 g of compound 1-353 was dissolved in 10 ml of ethyl 2-bromo- propionate, and the mixture was stiπed at 100°C for 6 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 0.2 g of compound 1-420.
1H-NMR (250 MHz, CDC13): δ (ppm) 1.26 (3H, t, J = 7.2 Hz), 1.52 (3H, d, J = 6.9 Hz), 3.71 (3H, s), 4.12 (IH, br), 4.21 (2H, q, J = 7.2 Hz), 4.71 (IH, br), 6.75 (IH, d, J = 6.5 Hz), 7.17 (IH, d, J = 9.5 Hz), 8.06 (IH, d, J = 1.6 Hz)
Production Example 30
First, 0.3 g of compound 1-353 was dissolved in 5 ml of pyridine, to which 0.5 ml of methanesulfonyl chloride was added, and the mixture was stiπed at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated, after which the pyridine was removed by azeotropic distillation with toluene. The residue was subjected to preparative thin layer chromatography, which afforded 0.3 g of compound 1-367.
1H-NMR (250 MHz, CDCI3): δ (ppm) 3.06 (3H, s), 3.74 (3H, s), 6.85 ( IH, br), 7.30 (IH, d, J = 9.1 Hz), 7.84 (IH, d, J = 6.9 Hz), 8.1 1 (IH, d, J = 1.4 Hz)
Production Example 31
First, 0.3 g of compound 1-353 was dissolved in 5 ml of pyridine, to which 5 ml of acetic anhydride was added, and the mixture was stiπed at room temperature for 5 hours. After completion of the reaction, toluene was added to the reaction mixture, which was concentrated. The precipitated crystals were recrystallized from hexane-ethyl acetate, which afforded 0.27 g of compound 1-669. 1H-NMR (250 MHz, CDC13): δ (ppm) 2.24 (3H, s), 3.73 (3H, s), 7.25 ( IH, d, J = 8.4 Hz), 7.51 (IH, br), 8.08 (IH, s), 8.51 (IH, d, J = 7.1 Hz)
Production Example 32
First, 0.18 g of sodium hydride (60% in oil) was suspended in 10 ml of N,N-dimethylformamide, to which 10 ml of a solution containing 1.0 g of compound 1-1014 in N,N-dimethylformamide was added dropwise at 5°C. The reaction mixture was warmed to room temperature and stirred for 1.5 hours, to which 0.5 ml of methyl iodide was added dropwise. The stirring was further continued at room temperature for 4.5 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.37 g of 5-(4-chloro-2-fluoro-5-isopropoxyphenyl)-4- methoxy-2-trifluoromethylpyrimidine, m.p. 77.8°C, and 0.23 g of compound 1-476.
Production Example 33
First, 0.5 ml of t-butyl nitrite, 3.3 ml of ethyl acrylate, and 0.5 g of copper (II) chloride were poured into 25 ml of acetonitrile, followed by cooling to 0°C, to which 10 ml of a solution containing 1.0 g of compound 1-353 in acetonitrile was slowly added dropwise, and the mixture was stirred at 0°C for 3 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 0.5 g of compound 1 -713.
•H-NMR (250 MHz, CDCI3): δ (ppm) 1.27 (3H, t, J = 7.2 Hz), 3.28 (IH, dd, J = 8.3, 14.2 Hz), 3.52 ( I H, dd, J = 6.5, 14.2 Hz), 3.73 (3H, s), 4.22 (V2 x 2H, q, J = 7.2 Hz), 4.23 (]/2 x 2H, q, J = 7.2 Hz), 4.56 ( I H, dd, J = 6.5, 8.3 Hz), 7.26 ( I H, d, J = 9.7 Hz), 7.51 ( I H, d, J = 7.6 Hz), 8.07 (IH, d, J = 1.4 Hz)
Production Example 34
First, 0.5 g of compound 1-353 was dissolved in 5 ml of ethyl bromoacetate, and the solution was stiπed at 100°C for 9 hours. After completion of the reaction, the reaction mixture was allowed to stand for cooling to room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.25 g of compound 1-380.
1H-NMR (300 MHz, CDC13): δ (ppm) 1.30 (3H, t, J = 7.1 Hz), 3.72 (3H, s), 3.94 (2H, s), 4.26 (2H, q, J = 7.1 Hz), 4.85 (IH, br), 6.70 (IH, d, J = 6.5 Hz), 7.18 (IH, d, J = 9.4 Hz), 8.08 (IH, d, J = 1.5 Hz)
Production Example 35
First, 7.5 ml of water and 7.5 ml of concentrated hydrochloric acid were added to 2.15 g of compound 1 -353, and the mixture was stiπed at 50°C for 1 -2/3 hours and then cooled to 5°C, to which a solution of 0.5 g of sodium nitrite in 10 ml of water was slowly added dropwise, and the mixture was further stiπed at 5°C for 50 minutes. The solution of a diazonium salt thus formed was added dropwise to a solution of 25 g of potassium iodide in 50 ml of water at room temperature, and the mixture was further stiπed at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was recrystallized from hexane-ethyl acetate, which afforded 1.93 g of compound 1-714, m.p. 156.8°C.
Production Example 36
First, 0.5 g of compound 1-714 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 5 ml of ethanol, 1.0 ml of diethylamine, and 0.1 g of dichlorobis- (triphenylphosphine)palladium were added, and carbon monoxide was bubbled into the mixture at room temperature for 13 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.19 g of compound 1-642.
1H-NMR (250 MHz, CDC13): δ (ppm) 1.40 (3H, t, J = 7.1 Hz), 3.74 (3H, s), 4.40 (2H, q, J = 7.1 Hz), 7.32 (IH, d, J = 9.6 Hz), 8.10 (IH, d, J = 7.7 Hz), 8.10 ( IH, d, J = 1.2 Hz)
Production Example 37
First, 0.9 g of compound 1-714 was dissolved in 10 ml of N,N-dimethyl- formamide, to which 2.5 g of sodium formate and a catalytic amount of dichlorobis- (triphenylphosphine)palladium were added, and carbon monoxide was bubbled into the mixture at room temperature for 25.5 hours. After completion of the reaction, the reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.22 g of compound 1-656, m.p. 158.6°C. H-NMR (250 MHz, CDCI3): δ (ppm) 3.74 (3H, s), 7.33 (IH, d, J = 9.3 Hz), 8.09 ( I H, s), 8.12 (IH, d, J = 7.8 Hz), 10.42 (IH, s)
Production Example 38
First, 0.15 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.2 g of potassium carbonate and 0.2 ml of cyclopentyl bromide were added, and the reaction was allowed to proceed at room temperature for 21 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to preparative thin layer chromatography, which afforded 0.14 g of compound 1-480, m.p. 101.6°C.
Production Example 39
First, 1.5 g of compound 1 -391 was dissolved in 15 ml of N,N-dimethyl- formamide, to which 1.5 g of potassium carbonate and 0.7 ml of methallyl chloride were added, and the reaction was allowed to proceed at room temperature for 19 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The resiude was subjected to silica gel column chromatography, which afforded 0.8 g of compound 1-715.
1H-NMR (250 MHz, CDC13): δ (ppm) 1.85 (3H, s), 3.73 (3H, s), 4.49 (2H, s), 5.02 (IH, d, J = 1.3 Hz), 5.14 (IH, d, J = 1.3 Hz), 7.15 (IH, d, J = 6.4 Hz), 7.24 (IH, d, J = 9.3 Hz), 8.11 (IH, d, J = 1.8 Hz)
Production Example 40
First, 0.33 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.23 g of potassium carbonate and 0.3 ml of 2,3-dichloropropene were added, and the reaction was allowed to proceed at room temperature for 1 hour. After completion of the reaction, the reaciton mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to thin layer chromato¬ graphy, which afforded 0.05 g of comound 1-483.
1H-NMR (250 MHz, CDCI3): δ (ppm) 3.74 (3H, s), 4.64 (2H, s), 5.49 (IH, d, J = 1.1 Hz), 5.66 (IH, d, J = 1.1 Hz), 7.20 (IH, d, J = 6.4 Hz), 7.27 (IH, d, J = 9.4 Hz), 8.12 (IH, d, J = 1.7 Hz)
Production Example 41
First, 0.33 g of compound 1-391 was dissolved in 5 ml of N,N-dimethyl- formamide, to which 0.3 g of potassium carbonate and 0.3 g of chloromethyl ethyl ether were added, and the reaction was allowed to proceed at room temperature for 30 minutes. After completion of the reaction, the reaciton mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to thin layer chromato¬ graphy, which afforded 0.3 g of comound 1-493.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.24 (3H, t, J = 7.1 Hz), 3.73 (3H, s), 3.79 (2H, q, J = 7.1 Hz), 5.28 (2H, s), 7.24 (IH, d, J = 9.36 Hz), 7.40 (IH, d, J = 6.6 Hz), 8.09 (IH, d, J = 1.4 Hz)
Production Example 42
First, 0.3 g of compound 1-391 was dissolved in 2 ml of dimethylsulfoxide, to which 1 ml of acetic anhydride was added, and the reaction was allowed to proceed at room temperature for 18 hours. After completion of the reaction, the reaciton mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 0.13 g of comound 1-494, m.p. 126.8°C.
Some of the present compounds are shown with their compound numbers in Tables 1 to 5, where the symbol "n" refers to normal-; "i", iso-; and "c", cyclo-.
TABLE 1
Compounds of the formula:
TABLE 1 (contn'd)
TABLE 1 (contn'd^)
TABLE 1 (contn'd
TABLE 1 (contn'd)
Compound No. Y R1 R R B
TABLE 1 (contn'd
87
TABLE 1 (cnntn'ri)
TABLE 1 (contn'd)
TABLE 1 (cont '
TABLE 1 fcontn'd)
TABLE 1 (contn'd
Compound - y R' R2 R3 B
No .
SCH(CH 3 )C00 n C3 H 7 SCH(CH 3 )C00 n C4 H 9 SCH(CH 3 )C00 n Cs H ,, SCH(CH 3 )C00 J C3 H 7 SCH(CH 3 )C00 c C5 H 9 SCH(CH 3 )C00 c C6 H SCH2 C0N(CH3 ) 2 SCH2 C0N(C 2 H 5 ) 2
SCH2CON( etramethylene)
SCH2CON(pentamethylene)
SCH2CON
( ethyleneoxyethylene )
-233 H Cl H CH3 CH3 SCH(CH3)CON
(pentamethylene'
TABLE 1 (contn'd
TABLE 1 icontn'd
TABLE 1 (contn'd)
► IΛ f
V n o 3 rt- 3^
CL
TABLE 1 (contn'd)
Compound ^ γ R > P
R B
CH=CHC00CH 3 CH=CHC00C2 H s CH2 CH2 COOCH 3 CH2 CH2 C00C2 H 5
H
H
H
H
H
H
H
H
H
H
H H
TABLE 1 (contn'd
TABLE 1 (contn'd)
Compound X Y R1 R R B No.
TABLE 1 (contn'd)
TABLE 1 (contn'dl
TABLE 1 (contn'd
Compound No. Y R1 R R B
TABLE 1 (contn'd
TABLE 1 (contn'd)
TABLE 1 (contn'd
TABLE 1 (contn'd
TABLE 1 (contn'd
Compound No . X Y R R R B
SCH2 COO n C 4 H 3 SCH2 COO n C s H ,, SCH2 COO i C 3 H 7 SCH2 COO c C s H 9 SCH2 COO c C 6 H ,, SCH(CH 3 )COOCH 3 SCH(CH 3 )C00C 2 H s SCH(CH 3 )C00 n C3 H 7 SCH(CH 3 )C00 n C 9 SCH(CH 3 )C00 n Cs H ,, SCH(CH 3 )C00 l Zo H 7 SCH(CH 3 )C00 c Cs H s SCH(CH 3 )C00 c CB H ii SCH2 C0N(CH3 ) 2 SCH2 C0N(C 2 H s ) 2
SCH2CON(tetramethylene)
SCH2CON(pentamethylene)
SCH2CON
(ethyleneoxyethylene)
-560 H Cl H CP3 CH3 SCH(CH3 )C0N(CH 3 ) 2 ■561 H Cl H CF3 CH3 SCH(CH3 )C0N(C2 H s ) 2 ■562 H Cl H CF3 CH3 SCH ( CH3 ) CON
( tetramethylene ) TABLE 1 (contn'd)
TABLE 1 (contn'd)
Compound - Y J-J ι ^ 2 -^ B No.
SCH(CH 3 )C00C 2 H 5
SCH(CH 3 )C00 n C3 H 7
SCH(CH 3 )C00 n C4 H 3
SCH(CH 3 )C00 n Cs H M
SCH(CH 3 )C00 J C3 H 7
SCH(CH 3 )C00 c Cs H 9
SCH(CH 3 )C00 c C6 H ., SCH2 C0N(CH3 ) 2
SCH2 C0N(C 2 H s ) 2 SCH2CON ( tetramethylene ) SCH2CO ( entamethylene )
SCH2CON
( ethyleneoxyethylene )
-597 F Cl H CF3 CH3 SCH(CH3 )C0N(CH 3 ) 2 -598 F Cl H CF3 CH3 SCH(CH3 )C0N(C2 H s ) 2 -599 F Cl H CF3 CH3 SCH(CH3)CON
( tetramethylene )
-600 Cl H CF3 CH: SCH(CH3)CON
( pentamethylene )
-601 H F H CF3 CH3 S02 Cl -602 H Cl H CF3 CH3 S02 Cl -603 H Br H CF3 CH3 S02 Cl
TABLE 1 (contn'd
TABLE 1 fcontn'd
TABLE 2
Compounds of the formula:
TABLE 2 (contn'd)
Compound χ z> n R. R2 R 3 R R No.
TABLE 2 (contn'dl
Compound x z' n R1 R2 R3 R4 R
No.
H H H H H H H H H H H H H H H H H H H H H H H TABLE 2 fcontn'
17
TABLE 2 (contn'd
Compound χ z * R , R 2 R 3 R 4 R
No .
TABLE 2 (contn'd^
Compound X Z * n R > R = R = R < R
No .
CH2 CC1 =CH2 CH2 C ≡CH CH(CH 3 )C≡CH CH2 CN CH2 OCH 3 CH20C2 H s CH2 COOH CH2 COOCH 3 CH2 C00C2 H s CH2 C00 " C 3 H 7 CH2 C00 n C 4 H 9 CH2 C00 " C 5 H ,, CH2 C00 < C 3 H 7 CH2 C00 c C s H a CH2 C00 c C 6 H ,ι CH(CH 3 )C00H CH(CH 3 )COOCH 3 CH(CH 3 )C00C a H s CH(CH3 )C00n C 3 H 7 CH(CH3 )C00" C 4 H 9 CH(CH3 )C00" C s H i. CH(CH3 )C00i C 3 H 7 CH(CH3 )C00C C s H 8 TABLE 2 (contn'd)
Compound χ ∑ l n R 1 R 2 R 3 R 4 R
No .
CH(CH3 )C00C C 6 H ,, H CH3 C2 H s
"C 3 H 7
"C 4 H 9
'C 3 H 7
'C 4 H 9
CH2 CH2 Cl
CH2 CH2 Br
CH2 CH=CH2
CH(CH 3 )CH =CH2
CH2 CC1 =CH2
CH2 C ≡CH
CH(CH 3 )C≡CH
CH2 CN
CH2 OCH 3
CH20C2 H s
CH2 COOH
CH2 COOCH 3 CH2 COOC2 H 5 CH2 COO " C 3 H 7 CH2 COO " C 4 H 9 TABLE 2 (contn'd)
TABLE 2 (contn'd)
TABLE 2 (contn'd)
Compound χ Z* n R* R=> R3 R4 R
No.
TABLE 2 (contn'd)
Compound X Z * n R > R* R= R« R
No .
1
TABLE 2 (contn'd)
TABLE 2 (contn'd)
Compound No. X Z1 n R R R R R
TABLE 2 (contn'd)
Compound X Z > n R > R' R3 R4 R No.
"C 3 H 7
"C 4 H 9
'C 3 H 1
XC 4 H 9
CH2 CH2 Cl
CH2 CH2 Br
CH2 CH=CH2
CH(CH 3 )CH =CH2
CH2 CC1 =CH2
CH2 C ≡CH
CH(CM 3 )C≡CH
CH2 CN
CH2 OCH 3
CH20C2 H s
CH2 COOH
CH2 COOCH 3 CH2 C00C2 H s CH2 C00 " C 3 H 7 CH2 C00 " C 4 H 9 CH2 C00 " C s H u CH2 C00 * C 3 H.7 CH2 C00 c C s H 9 CH2 C00 c C 6 H ,, TABLE 2 (contn'd)
TABLE 2 (contn'd)
TABLE 2 (contn'd)
Compound X Z ' π R ' R2 R3 R R No.
CH3 C2 H s
"C 3 H 7
"C 4 H 9
XC 3 H 7 αC 4 H 9
CH2 CH = CH2 CH(CH a )CH = CH2 CH2 C ≡CH CH(CH 3 )C≡CH CH2 OCH 3 CH2 0C2 H s
H
CH3 C2 H s
"C 3 H 7 "C 4 H 9
CH2 CH = CH2
CH(CH 3 )CH =CH2 CH2 C ≡CH CH(CH 3 )C≡CH CH2 OCH 3 CH2 0C2 H 5 TABLE 3
Compounds of the formula:
TABLE 3 (contn'd)
H i> W r* w > o o
3
TABLE 3 (contn'd)
TABLE 3 (contn'd)
TABLE 3 (contn'd)
> W tr1 w
OJ
O o 3
TABLE 3 (contn'd)
TABLE 3 (contn'd)
Compound χ γ Z2 R1 R2 R3 R
No .
TABLE 4
Compounds of the formula:
TABLE 4 (contn'd)
TABLE 4 (contn'd)
Compound χ γ Rι R2 RO R R No.
COOC2 H
C00 C 3 H 7 C00 C 4 H 9 C00 C 5 H 1 1 C00 C 3 H 7 C00 C 5 H a C00 C ε H 1 1
C00CH2 CH=CH2 COOCH2 C ≡ CH
C0NH2
CONHCH3 C0NHC2 H s
C0N(CH3 ) 2 C0N(C2 H s ) 2
CH2 Cl
CH2 Br
CH2 OCH 3
CH20C2 H s CH2 OCH 2 OCH 3 CH2 OCH 2 OC 2 Hs
CH2 OCOCH 3
CH2 OCOC a Hs CH20C0 ' C 3 H 7 TABLE 4 (contn'ri
TABLE 4 (contn'ri
TABLE 4 (contn'd
Compound X Y R ' R 2 R 3 R R
No.
TABLE 4 (contn'ril
TABLE 4 (contn'ri
TABLE 4 (contn'd^
TABLE 4 (contn'd)
Compound No. X Y R1 R R R7 R
TABLE 4 (contn'd)
TABLE 5
Compounds of the formula:
TABLE 5 (contn'd)
The following will describe production examples for compound [2] which is an intermediate compound for the production of the present compounds.
Intermediate Production Example 1
First, 7.5 g of ethyl E- and Z-2-(4'-chlorophenyl)-3-methoxyacrylate was dissolved in 180 ml of ethanol, to which 1 1.0 g of acetamidine hydrochloride and 16.1 g of potassium carbonate were added, and the mixture was stirred at 60°C for 2.5 hours. The reaction mixture was cooled to room temperature, neutralized by the addition of acetic acid, and concentrated. The precipitated crystals were collected by filtration, washed with water, and dried, which afforded 6.5 g of compound 1-1002.
'H-NMR (60 MHz, DMSO-d6): δ (ppm) 2.30 (3H, s), 7.35 (2H, d, J = 9 Hz), 7.70 (2H, d, J = 9 Hz), 8.05 (IH, s)
Intermediate Production Example 2
First, 2.8 g of ethyl E- and Z-2-(2',4'-difluorophenyl)-3-methoxyacrylate was dissolved in 70 ml of ethanol, to which 4.1 g of acetamidine hydrochloride and 6.0 g of potassium carbonate were added, and the mixture was stirred at 60°C for 3 hours. The reaction mixture was cooled to room temperature, neutralized by the addition of acetic acid, and concentrated. The precipitated crystals were collected by filtration, washed with water, and dried, which afforded 2.0 g of compound 1-1004.
Intermediate Production Example 3
First, 1.5 ml of trifluoroacetamidine was added to 1.0 g of ethyl 2-(4'-chloro- phenyl)-2-formylacetate, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was subjected to silica gel chromato¬ graphy, which afforded 0.3 g of compound 1-1008.
•H-NMR (60 MHz, CDC13 + DMSO-d6): δ (ppm) 7.30 (2H, d, J = 9 Hz), 7.55 (2H, d, J = 9 Hz), 8.30 (IH, s)
Intermediate Production Example 4
First, 1.0 ml of trifluoroacetamidine was added to 1.0 g of ethyl E- and Z-2- (4'-chlorophenyl)-3-methoxyacrylate, followed by stirring for 3 hours, to which 0.5 ml of trifluoroacetamidine was further added, and the mixture was stirred at 60°C for 4 hours. The reaction mixture was cooled to room temperature and subjected to silica gel chromatography, which afforded 0.8 g of compound 1-1008. The physical properties are the same as those obtained in Intermediate Production Example 3.
Intermediate Production Example 5
First, 5.0 ml of trifluoroacetamidine was added to 5.0 g of ethyl 2-(2',4'- difluorophenyl)-2-formylacetate, and the mixture was stirred at room temperature for 17 hours. After completion of the reaction, the reaction mixture was subjected to silica gel chromatography, which afforded 0.5 g of compound 1-1010.
1H-NMR (250 MHz, CDC13 + DMSO-d6): δ (ppm) 6.80-7.00 (2H, m), 7.45-7.55 ( I H, m), 7.94 (IH, s)
Intermediate Production Example 6
First, 7 ml of trifluoroacetamidine was added to 6.9 g of ethyl E- and Z-2- (2\4'-difluorophenyl)-3-methoxyacrylate, and the mixture was stirred at room tempera¬ ture for 23 hours. After completion of the reaction, the reaction mixture was subjected to silica gel chromatography, which afforded 3.9 g of compound 1-1010. The physical properties are the same as those obtained in Intermediate Production Example 5.
Intermediate Production Example 7
First, 5.15 g of ethyl E- and Z-2-(2',4'-dichlorophenyl)-3-methoxyacrylate was dissolved in 150 ml of ethanol, to which 6.08 g of acetamidine hydrochloride and 1 1.02 g of potassium carbonate were added, and the mixture was stirred at 60°C for 3.5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, neutralized by the addition of acetic acid, and concentrated. The precipitated crystals were collected by filtration and dried, which afforded 4.35 g of compound 1 -1013, m.p. 250°C or higher (decomp.).
Intermediate Production Example 8
First, 10 ml of trifluoroacetamidine was added to 2.2 g of ethyl (E- and Z-) 2-(4'-chloro-2'-fluoro-5'-isopropoxy)-3-methoxyacrylate, and the mixture was stirred at room temperature for 28 hours. After completion of the reaction, the reaction mixture was subjected to silica gel column chromatography, which afforded 2.0 g of compound 1 -1014. H-NMR (250 MHz, CDC13): 5 (ppm) 1.34 (6H, d, J = 6.0 Hz), 4.44 (IH, hp, J = 6 Hz), 6.82 (IH, d, J = 6.6 Hz), 7.00 (IH, d, J = 7.8 Hz), 8.18 (IH, s)
Intermediate Production Example 9
First, 5 ml of trifluoroacetamidine was added to 4.0 g of ethyl E- and Z-2- (4'-fluorophenyl)-3-methoxyacrylate, and the reaction was allowed to proceed at room temperature for 47 hours. After completion of the reaction, the reaction mixture was subjected to silica gel column chromatography, which afforded 3.5 g of compound 1 -1007.
1H-NMR (250 MHz, CDCI3): δ (ppm) 7.05 (2H, dd, J = 9.7, 9.7 Hz), 7.62 (2H, dd, J = 5.5, 9.7 Hz), 8.23 (IH, s)
Intermediate Production Example 10
First, 5.0 ml of trifluoroacetamidine was added to 3.0 g of ethyl E- and Z-2- (2',4'-dichlorophenyl)-3-methoxyacrylate, and the reaction was allowed to proceed for 5 days. After completion of the reaction, the reaction mixture was subjected to silica gel column chromatography, which afforded 3.5 g of compound 1-1015 as a crude product.
Intermediate Production Example 11
First, 50 g of trifluoroacetamidine was added to 34 g of ethyl E- and Z-2-(4'- chloro-2'-fluorophenyl)-3-methoxyacrylate, and the reaction was allowed to proceed for 4 days. After completion of the reaction, the reaction mixture was subjected to silica gel column chromatography, which afforded 25.6 g of compound 1-101 1.
>H-NMR (250 MHz, CDCI3): δ (ppm) 7.05-7.12 (2H, m), 7.40 (IH, dd, J = 7.9, 7.9 Hz), 8.21 (IH, d, J = 1.2 Hz)
Examples of compound [2] are shown with their compound numbers in Tables 6 to 8. TABLE 6
Compound of the formula:
TABLE 7
Compound of the formula:
TABLE 7 (contn ^
Compound Y R No. X R R
P96/02169
163
TABLE 8
Compound of the formula:
TABLE 8 (contn'd
Compound No. Y R R R R
TABLE 8 (contn'd)
The following will describe production examples for compounds [5] and [27] which are starting compounds for the production of the present compounds.
Reference Example 1
Production of ethyl 2-(4'-chlorophenyl)-2-formylacetate and ethyl E- and Z-2-(4'-chlorophenyl)-3-methoxyacrylate
First, 17.24 g of 4-chlorophenylacetic acid was dissolved in 200 ml of ethanol, to which a catalytic amount of p-toluenesulfonic acid was added, and the mixture was heated under reflux for 10 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and concentrated. The residue was poured into water and extracted with ethyl acetate, and the organic layer was dried and then concen¬ trated. The residue was subjected to silica gel chromatography, which afforded 19.0 g of ethyl 4-chlorophenylacetate.
Then, 4.19 g of sodium hydride (60% in oil) was suspended in 150 ml of tetrahydrofuran, to which a solution of 19.0 g of ethyl 4-chlorophenylacetate in 150 ml of tetrahydrofuran was added dropwise at 5° to 10°C. After stirring at room temperature for 1.5 hours, 8.42 g of ethyl formate was added, and the mixture was further stirred at room temperature for 4.5 hours. After completion of the reaction, the reaction mixture was cooled to ice temperature, neutralized by the addition of diluted hydrochloric acid, and concentrated. The residue was subjected to phase separation with ethyl acetate- water, and the organic layer was dried and then concentrated. The residue was subjected to silica gel chromatography, which afforded 17.0 g of ethyl 2-(4'-chlorophenyl)-2- formylacetate.
Then, 1.93 g of sodium hydride (60% in oil) was suspended in 90 ml of 1 ,2-dimethoxyethane, to which 90 ml of a solution of ethyl 2-(4'-chlorophenyl)-2-formyl- acetate was added dropwise at 5° to 10°C After stirring at room temperature for l - ]/3 hours, 1 1.76 g of methyl iodide was added dropwise, and the mixture was further stirred at room temperature for 20 hours. After completion of the reaction, the reaction mixture was cooled with ice, and excess sodium hydride was decomposed by the addition of water, followed by extraction with ethyl acetate-water. The organic layer was dried and then concentrated, and the residue was subjected to silica gel chromatography, which afforded 7.58 g of ethyl E- and Z-2-(4'-chlorophenyl)-3-methoxyacrylate.
Reference Example 2
Production of ethyl 2-(2',4'-difluorophenyl)-2-formylacetate and ethyl E- and Z-2-(2',4'-difluorophenyl)-3-methoxyacrylate
Ethyl 2-(2',4'-difluorophenyl)-2-formylacetate and ethyl E- and Z-2-(2',4'-di- fluorophenyl)-3-methoxyacrylate were synthesized with 2,4-difluorophenylacetate as the starting compound in the same manner as described in Reference Example 1.
Reference Example 3
Production of ethyl 2-(2',4'-dichlorophenyl)-2-formylacetate and ethyl E- and Z-2-(2',4'-dichlorophenyl)-3-methoxyacrylate
Ethyl 2-(2',4'-dichlorophenyl)-2-formylacetate and ethyl E- and Z-2-(2',4'-di- chlorophenyl)-3-methoxyacrylate were synthesized with 2,4-dichlorophenylacetate as the starting compound in the same manner as described in Reference Example 1.
Reference Example 4
Production of ethyl 2-(4-chloro-2-fluoro-5-isopropoxyphenyl)-2-formyl- acetate and ethyl (E- and Z-) 2-(4'-chloro-2'-fluoro-5'-isopropoxy)-3-methoxyacrylate
( 1 ) First, 250 ml of water and 25 ml of concentrated sulfuric acid were added to 30 g of 4-chloro-2-fluoro-5-isopropoxyaniline, and the mixture was stirred at 50°C for 2.5 hours and then cooled to 0°C, to which a solution of 10.4 g of sodium nitrite in 80 ml of water was slowly added dropwise. The solution of a diazonium salt thus formed was added dropwise to a solution of 150 g of potassium iodide in 300 ml of water at room temperature, and the mixture was stirred for at room temperature for 45 minutes. After completion of the reaction, the reaction mixture was extracted with diethyl ether, and the organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 36 g of 2-chloro-4-fluoro-5-iodo-l-isopropoxybenzene. 1H-NMR (250 MHz, CDC1 ): δ (ppm) 1.36 (6H, d, J = 6.2 Hz), 4.46 (IH, hp, J = 6.2 Hz), 7.1 1 ( IH, d, J = 7.2 Hz), 7.27 (IH, d, J = 5.7 Hz)
(2) Then, 62.9 g of 2-chloro-4-fluoro-5-iodo-l-isopropoxybenzene, 20.4 g of sodium formate, and 2.81 g of dichlorobis(triphenylphosphine)palladium were dissolved in 120 ml of N,N-dimethylformamide, which was stirred at 90° to 100°C for 12 hours, while bubbling carbon monoxide thereinto. After completion of the reaction, the reaction mixture was cooled to room temperature, to which diluted hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 15 g of 4-chloro-2- fluoro-5-isopropoxybenzaldehyde.
1H-NMR (300 MHz, CDCI3): 6 (ppm) 1.31 (6H, d, J = 6.3 Hz), 4.52 (IH, hp, J = 6.3 Hz), 7.18 (IH, d, J = 9.7 Hz), 7.29 (IH, d, J = 6.1 Hz), 10.2 (IH, s)
(3) Then, 7.5 g of 4-chloro-2-fluoro-5-isopropoxybenzaldehyde was dissolved in 70 ml of 1,4-dioxane and 5 ml of methanol, to which 0.92 g of sodium borohydride was added at 5°C, and the mixture was stirred for 40 minutes. After completion of the reaction, a small amount of diluted hydrochloric acid was added, and the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 6.7 g of 4-chloro-2-fluoro-5-isopropoxybenzyl alcohol.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.36 (6H, d, J = 6.0 Hz), 1.96 (IH, br), 4.49 ( I H, hp, J = 6.0 Hz), 4.71 (IH, d, J = 5.2 Hz), 7.04 (IH, d, J = 6.7 Hz), 7.09 (IH, d, J = 9.2 Hz)
(4) Then, 6.7 g of 4-chloro-2-fluoro-5-isopropoxybenzylalcohol was dissolved in 70 ml of tetrahydrofuran, to which 1 ml of pyridine was added, and the mixture was cooled to 5°C Then, 5 ml of thionyl chloride was slowly added dropwise at 5° to 10°C, and the mixture was stirred at 5°C for 1.5 hours. After completion of the reaction, the reaction mixture was filtered to separate the precipitated crystals, and the filtrate was concentrated. The residue was subjected to silica gel column chromato¬ graphy, which afforded 7.3 g of 4-chloro-2-fluoro-5-isopropoxybenzyl chloride. -NMR (300 MHz, CDC13): δ (ppm) 1.37 (6H, d, J = 6.0 Hz), 4.49 (IH, hp, J = 6.0 Hz), 4.57 (2H, s), 6.99 (IH, d, J = 6.8 Hz), 7.13 (IH, d, J = 9.2 Hz)
(5) Then, 7.3 g of 4-chloro-2-fluoro-5-isopropoxybenzyl chloride was dissolved in 70 ml of ethanol and 30 ml of water, to which 1.8 g of sodium cyanide was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which 7.0 g of 4-chloro-2-fluoro-5-isopropoxyphenylacetonitrile.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.38 (6H, d, J = 5.9 Hz), 3.73 (2H, s), 4.51 (IH, hp, J = 5.9 Hz), 7.00 (IH, d, J = 6.8 Hz), 7.16 (IH, d, J = 9.0 Hz)
(6) Then, 7.0 g of 4-chloro-2-fluoro-5-isopropoxyphenylacetonitrile was dissolved in 100 ml of ethanol, to which 5 ml of sulfuric acid, and the mixture was heated under reflux for 66 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 7.2 g of ethyl 4-chloro-2- fluoro-5-isopropoxyphenyl acetate.
Η-NMR (250 MHz, CDCI3): δ (ppm) 1.26 (3H, t, J = 7.1 Hz), 1.36 (6H, d, J = 6.0 Hz), 3.60 (2H, s), 4.17 (2H, q, J = 7.1 Hz), 4.46 ( IH, hp, J = 6.0 Hz), 6.87 ( IH, d, J = 6.8 Hz), 7.10 (IH, d, J = 9.0 Hz)
(7) Then, 1.1 g of sodium hydride (60% in oil) was suspended in 50 ml of tetrahydrofuran, and the mixture was cooled to 5°C, to which a solution of 7.2 g of ethyl 4-chloro-2-fluoro-5-isopropoxyphenylacetate in 80 ml of tetrahydrofuran was slowly added dropwise. The mixture was stirred for 30 minutes with a gradual temperature increase to room temperature, to which 10 ml of ethyl formate was added at room temperature, followed by stirring for 3 hours. Then, the reaction mixture was cooled to 5°C, to which diluted hydrochloric acid was added. The reaction mixture was concen¬ trated, and the residue was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 8.0 g of ethyl 2-(4-chloro-2-fluoro-5-isopropoxyphenyl)-2-formylacetate.
1H-NMR (300 MHz, CDC13): δ (ppm) 1.26 (3H, t, J = 7.0 Hz), 1.36 (6H, d, J = 6.2 Hz), 4.26 (2H, q, J = 7.0 Hz), 4.45 (IH, hp, J = 6.2 Hz), 6.76 <ll2H, s), 6.78 (V2H, s), 7.10 (IH, d, J = 8.9 Hz), 7.26 (IH, d, J = 12.6 Hz), 12.1 (V2H, s), 12.2 (V2H, s)
(8) Then, 1.1 g of sodium hydride (60% in oil) was suspended in 50 ml of 1 ,2-dimethoxyethane, and the mixture was cooled to 5°C, to which a solution of 8.0 g of ethyl 2-(4-chloro-2-fluoro-5-isopropoxyphenyl)-2-formylacetate in 50 ml of 1,2-di- methoxyethane was slowly added dropwise. The mixture was stirred for 20 minutes with a gradual temperature increase to room temperature, to which 3.0 ml of methyl iodide was added at room temperature, followed by stirring for 4.5 hours. Then, the reaction mixture was cooled to 5°C, to which diluted aqueous hydrochloric acid was added. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concen¬ trated. The residue was subjected to silica gel column chromatography, which afforded 5.5 g of ethyl (E- and Z-)2-(4'-chloro-2'-fluoro-5'-isopropoxyphenyl)-3-methoxy- acrylate.
Reference Example 5
Production of ethyl E- and Z-2-(4'-fluorophenyl)-3-methoxyacrylate
Ethyl E- and Z-2-(4'-fluorophenyl)-3-methoxyacrylate was synthesized with 4-fluorophenylacetate as the starting compound in the same manner as described in Reference Example 1. Reference Example 6
Production of ethyl E- and Z-2-(4'-chloro-2'-fluorophenyl)-3-methoxy- acrylate
( 1 ) First, 25 g of 4-chloro-2-fluorobenzaldehyde was dissolved in a mixed solvent consisting of 250 ml of 1,4-dioxane and 25 ml of methanol, to which 2.4 g of sodium borohydride was added under ice cooling, and the mixture was stirred for 30 minutes. After completion of the reaction, a small amount of diluted aqueous hydrochloric acid was added, and the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 25 g of 4-chloro-2-fluorobenzyl alcohol.
1H-NMR (300 MHz, CDC13): δ (ppm) 1.82 (IH, t, J = 6.1 Hz), 4.72 (2H, d, J = 6.1 Hz), 7.08 (IH, dd, J = 2.1, 9.8 Hz), 7.15 ( IH, dd, J = 2.1 , 8.2 Hz), 7.37 (IH, dd, J = 8.2, 8.2 Hz)
(2) Then, 16.5 g of 4-chloro-2-fluorobenzylalcohol was dissolved in 150 ml of tetrahydrofuran and 1 ml of pyridine, to which 10 ml of thionyl chloride was added dropwise at 5°C, and the mixture was stirred for 2-5/(, hours. After completion of the reaction, the reaction mixture was concentrated, and the precipitated crystals were collected by filtration. The filtrate was subjected to silica gel column chromatography, which afforded 18.5 g of 4-chloro-2-fluorobenzyl chloride. H-NMR (250 MHz, CDCI3): δ (ppm) 4.59 (2H, s), 7.09-7.17 (2H, m), 7.36 ( IH, dd, J = 7.9, 7.9 Hz)
(3) Then, 18.5 g of 4-chloro-2-fluorobenzyl chloride was dissolved in a mixed solvent consisting of 130 ml of ethanol and 30 ml of water, to which 5.3 g of sodium cyanide was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture was allowed to stand for cooling to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 15.1 g of 4-chloro-2- fluorophenylacetonitrile. -NMR (250 MHz, CDC13): δ (ppm) 3.74 (2H, s), 7.12-7.22 (2H, m), 7.39 (IH, dd, J = 8.0, 8.0 Hz)
(4) Then, 15.1 g of 4-chloro-2-fluoroacetonitrile was dissolved in 150 ml of ethanol, to which 10 ml of sulfuric acid was added, and the mixture was heated under reflux for 65 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 17.8 g of ethyl 4-chloro-2-fluorophenyl- acetate.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.25 (3H, t, J = 7.1 Hz), 3.63 (2H, s), 4.17 (2H, q, J = 7.1 Hz), 7.07-7.24 (3H, m)
(5) Then, 3.6 g of sodium hydride (60% in oil) was suspended in 120 ml of tetrahydrofuran, and the mixture was cooled to 5°C, to which a solution of 17.8 g of ethyl 4-chloro-2-fluorophenylacetate in 120 ml of tetrahydrofuran was slowly added drop- wise. The mixture was stirred for 30 minutes with a gradual temperature increase to room temperature, to which 20 ml of ethyl formate was added at room temperature, followed by stirring for 3 hours. Then, the reaction mixture was cooled with ice, to which diluted aqueous hydrochloric acid was added. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 19.1 g of ethyl 2-(4-chloro-2-fluoro- phenyl)-2-formylacetate.
1H-NMR (250 MHz, CDCI3): δ (ppm) 1.25 (l/2 x 3H, t, J = 7.1 Hz), 1.26 0/2 3H, t, J = 7.1 Hz), 4.26 (2H, q, J = 7.1 Hz), 7.07-7.26 (3H, m), 9.74 (>/2H, br), 9.80 (V2H, br)
(6) Then, 3.4 g of sodium hydride (60% in oil) was suspended in 120 ml of 1,2-dimethoxyethane, and the mixture was cooled to 5°C, to which a solution of 19.1 g of ethyl 2-(4-chloro-2-fluorophenyl)-2-formylacetate in 120 ml of 1,2-dimethoxy¬ ethane was slowly added dropwise. The mixture was stirred for 30 minutes with a gradual temperature increase to room temperature, to which 10 ml of methyl iodide at room temperature, and the mixture was stirred for 3- 1/3 hours. Then, the reaction mixture was cooled with ice, to which diluted aqueous hydrochloric acid was added. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated, The residue was subjected to silica gel column chromatography, which afforded 11.1 g of ethyl E- and Z-2-(4'-chloro-2'-fluorophenyl)-3-methoxyacrylate.
The following will describe formulation examples for the present compounds, where the present compounds are designated by their compound numbers shown in Tables 1 to 5 and parts are by weight.
Formulation Example 1
Fifty parts of each of compounds 1-1 to 1-715, 2-1 to 2-380, 3-1 to 3-256, 4- 1 to 4-272, and 5- 1 to 5-35, 3 parts of calcium ligninsulfonate, 2 parts of sodium laurylsulfate, and 45 parts of synthetic hydrated silicon oxide are well pulverized and mixed to give a wettable powder for each compound.
Formulation Example 2
Ten parts of each of compounds 1-1 to 1-715, 2-1 to 2-380, 3-1 to 3-256, 4- 1 to 4-272, and 5- 1 to 5-35, 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 35 parts of xylene, and 35 parts of cyclohexanone are well mixed to give an emulsifiable concentrate for each compound.
Formulation Example 3
Two parts of each of compounds 1- 1 to 1-715, 2-1 to 2-380, 3-1 to 3-256, 4-1 to 4-272, and 5- 1 to 5-35, 2 parts of synthetic hydrated silicon oxide, 2 parts of calcium ligninsulfonate, 30 parts of bentonite, and 64 parts of kaoline clay are well pulverized and mixed, to which water is added, and the mixture is well kneaded, granulated, and dried to give a granule for each compound.
Formulation Example 4
Twenty-five parts of each of compounds 1-1 to 1-715, 2-1 to 2-380, 3-1 to 3-256, 4-1 to 4-272, and 5-1 to 5-35, 50 parts of 10% aqueous polyvinyl alcohol solution, and 25 parts of water are mixed, and the mixture is pulverized until the average particle size becomes 5 μm or less to give a flowable for each compound.
The following test examples will demonstrate that the present compounds are useful as active ingredients of herbicides. The present compounds are designated by their compound numbers shown in Tables 1 to 5.
The herbicidal activity was evaluated at 6 levels with indices of 0 to 5, i.e., designated by the numeral "0", "1 ", "2", "3", "4" or "5", wherein "0" means that there was no or little difference in the degree of germination or growth between the treated and the untreated test plants at the time of examination, and "5" means that the test plants died complete or their germination or growth was completely inhibited. The herbicidal activity is excellent when rated at "4" or "5" but insufficient when rated at "3" or lower.
Test Example 1 : Foliar treatment on upland fields
Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, in which the seeds of velvetleaf (Abutilon theophrasti) were sowed, and the test plants were grown in a greenhouse for 15 days. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water containing a spreading agent to a prescribed concentration. The dilution was uniformly sprayed over the foliage of the test plants with a sprayer at a volume of 1000 liters per hectare. After the application, the test plants were grown in the greenhouse for 15 days, and the herbicidal activity was examined. The results are shown in Table 9. TABLE 9
Test Example 2: Soil surface treatment on upland fields Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, in which the seeds of velvetleaf (Abutilon theophrasti) were sowed. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water to a prescribed concentration. The dilution was uniformly sprayed over the soil surface in the pots with a sprayer at a volume of 1000 liters per hectare. After the application, the test plants were grown in a greenhouse for 19 days, and the herbicidal activity was examined. The results are shown in Table 10.
TABLE 10
Test Example 3: Flooding treatment on paddy fields
Cylindrical plastic pots of 9 cm in diameter and 1 1 cm in depth were filled with soil, in which the seeds of barnyardgrass (Echinochloa oryzicola) were sowed. These pots were flooded to form a paddy field, and the test plants were grown in a green- house for 7 days. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water to a prescribed concentration. The dilution was applied to the water surface in the pots with a syringe at a volume of 50 liters per are. After the application, the test plants were grown in the greenhouse for 19 days, and the herbicidal activity was examined. The results are shown in Table 1 1.
TABLE 11
Test Example 4: Foliar treatment on upland fields
Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, in which the seeds of velvetleaf (Abutilon theophrasti) and barnyardgrass (Echinochloa crus-galli) were sowed, and the test plants were grown in a greenhouse for 1 days. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water contain¬ ing a spreading agent to a prescribed concentration. The dilution was uniformly sprayed over the foliage of the test plants with a sprayer at a volume of 1000 liters per hectare. After the application, the test plants were grown in the greenhouse for 15 days, and the herbicidal activity was examined. The results are shown in Table 12. TABLE 12
Test Example 5: Soil surface treatment on upland fields Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, in which the seeds of velvetleaf (Abutilon theophrasti) and barnyardgrass (Echinochloa crus-galli) were sowed. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water to a prescribed concentration. The dilution was uniformly sprayed over the soil surface in the pots with a sprayer at a volume of 1000 liters per hectare. After the application, the test plants were grown in the greenhouse for 19 days, and the herbicidal activity was examined. The results are shown in Table 13. TABLE 13
Test Example 6: Flooding treatment on paddy fields
Cylindrical plastic pots of 9 cm in diameter and 1 1 cm in depth were filled with soil, in which the seeds of barnyardgrass (Echinochloa oryzicola) and hardstem bulrush (Scirpus juncoides) were sowed. These pots were flooded to form a paddy field, and the test plants were grown in a greenhouse for 7 days. Each of the test compounds listed below was formulated into an emulsifiable concentrate according to Formulation Example 2, which was diluted with water to a prescribed concentration. The dilution was applied to the water surface in the pots with a syringe at a volume of 50 liters per are. After the application, the test plants were grown in the greenhouse for 19 days, and the herbicidal activity was examined. The results are shown in Table 14. TABLE 14
Test Example 7: Foliar treatment on upland fields
Plastic pots of 26.5 x 19 cm2 in area and 7 cm in depth were filled with soil, in which the seeds of ivyleaf morningglory (Ipomoea hederacea), common cocklebur (Xanthium pensylvamcum), common ragweed (Ambrosia artemisiifolia), and barnyard¬ grass (Echinochloa crus-galli) were sowed and grown so that the application of a chemical to these weed species was made after 23, 27, 30, and 17 days from sowing, respectively. Each of the test compounds listed below was formulated into an emulsifi¬ able concentrate according to Formulation Example 2, which was diluted with water to a prescribed concentration. The dilution was uniformly sprayed over the foliage of the test plants with a sprayer at a volume of 1050 liters per hectare. At this time, the unfavorable weeds, although their growth stage was different depending upon the weed species, were at the 2- to 4-leaf stage, and the plant height was 8 to 18 cm. After 21 days from the application, the herbicidal activity was examined. The results are shown in Table 15. This test was made in a greenhouse over the test period. TABLE 15

Claims

CLAIMS 1 . A compound of the formula:
wherein R1 is hydrogen or C1-C3 alkyl; R2 is C1-C3 alkyl optionally substituted with one or more halogen atoms; R3 is C1-C6 alkyl optionally substituted with one or more halogen atoms, C3-C6 alkenyl, or C3-C6 alkynyl; and Q is substituted phenyl.
2. A compound according to claim 1 , wherein Q is [Q-1], [Q-2], [Q-3], [Q-4], or [Q-5] of the formula:
wherein X is hydrogen or halogen;
Y is halogen, nitro, cyano, or trifluoromethyl;
Z1 is oxygen, sulfur, NH, or methylene;
Z2 is oxygen or sulfur;
n is 0 or 1 ; B is hydrogen, halogen, nitro, cyano, chlorosulfonyl, -OR10, -SR10, -SO2- OR 10, -N(R10)R 1 1, -SO2N(R 1 1)R12, -NR1 1(COR13), -NR1 1(SO2R14), -N(SO2R14)-(SO2R 15), -N(SO2R14)(COR13), -NHCOOR13, -COOR13, -CON(Rn)R12, -CSN- (R 1 1)R 12, -COR16, -CR17=CR 1 8CHO, -CR17=CR 18COOR 13, CR17=CR 18CON- (R 1 1)R12, -CH2CHWCOOR13, or -CH2CHWCON(R1 1)R12, wherein W is hydrogen, chlorine or bromine; R10 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, cyano C1-C6 alkyl, C2-C8 alkoxyalkyl, C2-C8 alkylthioalkyl, carboxy C1-C6 alkyl, (C1-C6 alkoxy)- carbonyl C1-C6 alkyl, (C1-C6 haloalkoxy)carbonyl C1-C6 alkyl, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl, (C3-C8 cycloalkoxy)carbonyl C1-C6 alkyl, -CH2CON-(R11)R12, -CH2COON(R11)R12, -CH(C1-C4 alkyl)CON(R11)R12, or -CH(C1-C4 alkyl)-COON(R11)R12; R11 and R12 are independently hydrogen, C 1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, cyano C1-C6 alkyl, C2-C8 alkoxyalkyl, C2-C8 alkylthioalkyl, carboxy C1-C 6 alkyl, (C1-C6 alkoxy)carbonyl C1-C6 alkyl, or {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl, or R11 and R12 are taken together to form tetramethylene, pentamethylene, or ethyleneoxyethylene; R13 is hydrogen, C1-C6 alkyl, C1 -C6 haloalkyl, or C3-C8 cycloalkyl; R 14 and R15 are independently C1-C6 alkyl, C1-C6 haloalkyl, or phenyl optionally substituted with methyl or nitro; R16 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C8 alkoxyalkyl, or hydroxy C1-C6 alkyl; and R17 and R18 are independently hydrogen or C1-C6 alkyl;
R4 is hydrogen or C1-C3 alkyl,
R5 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, cyano C 1-C6 alkyl, C2-C8 alkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, carboxy C1-C6 alkyl, (C1-C6alkoxy)carbonyl C1-C6 alkyl, { (C1-C4 alkoxy) C 1-C4 alkoxy} carbonyl C1-C6 alkyl, (C3-C8 cycloalkoxy)carbonyl- C 1 -C6 alkyl, -CH2CON(R1 1)R12, -CH2COON(R11 )R12, -CH(C1 -C4 alkyl)CON(R1 1)R12, -CH(C1-C4 alkyl)COON(R1 1)R12, C2-C8 alkylthioalkyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, (C1-C 8 alkyl)carbonyl, (C1-C8 alkoxy)carbonyl, or hydroxy C1-C6 alkyl;
R 6 is C 1- C6 alkyl, C1-C 6 haloalkyl, formyl, cyano, carboxyl, hydroxy C 1 -C6 alkyl, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl, (C1-C6 alkyl)carbonyloxy C1-C6 alkyl, (C1-C6 haloalkyl)carbonyloxy C1-C6 alkyl, ( C1-C6 alkoxy )carbonyl, or (C1-C6 alkyl)carbonyl;
R7 is hydrogen or C1-C6 alkyl; and
R8 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C8 alkoxyalkyl, C3-C10 alkoxyalkoxyalkyl, (C1-C5 alkyl)carbonyloxy C1-C6 alkyl, (C 1-C6 haloalkyl)carbonyloxy C1-C6 alkyl, carboxyl, carboxy C1-C6 alkyl, (C1-C8 alkoxy)carbonyl, (C 1 -C6 haloalkoxy)carbonyl, (C3-C 1 0 cycloalkoxy)carbonyl, (C3-C8 alkenyloxy)carbonyl, (C3-C8 alkynyloxy)carbonyl, aminocarbonyl, (C1-C6 alkyI)aminocarbonyl, di(C 1 -C6 alkyl)aminocarbonyl, (C1-C6 alkyl)aminocarbonyloxy C1-C6 alkyl, or di(C 1-C6 alkyl)aminocarbonyloxy C1-C6 alkyl.
3. A compound according to claim 2, wherein Q is [Q-1], [Q-2], [Q-3], or [Q-4];
Y is halogen;
Z1 is oxygen or sulfur;
Z2 is oxygen;
B is hydrogen, nitro, -OR10, -SR 10, -NHR 10, -NHSO2R14, -COOR13, or -CH2CHWCOOR13, wherein W is hydrogen or chlorine; R10 is C1-C6 alkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, cyano C1-C6 alkyl, or (C1-C6 alkoxy)carbonyl C1-C6 alkyl; R13 is C1-C6 alkyl; and R14 is C1-C6 alkyl;
R5 is C1-C6 alkyl, C3-C6 alkenyl, or C3-C6 alkynyl;
R6 is C1-C6 alkyl, C1-C6 haloalkyl, formyl, hydroxymethyl, C1-C6 alkoxymethyl, C1-C6 alkylcarbonyloxymethyl, or C1-C6 alkoxy carbonyl;
R7 is hydrogen or methyl; and
R8 is methyl, hydroxymethyl, C1-C6 alkoxymethyl, (C1-C5 alkyl)carbonyl oxymethyl, carboxyl, or (C1-C6 alkoxy)carbonyl.
4. A compound according to claim 1, 2, or 3, wherein R2 is C 1-C3 alkyl substituted with one or more halogen atoms.
5. A compound according to claim 1, 2, or 3, wherein R2 is trifluoromethyl.
6. A compound according to claim 2, wherein Q is [Q-1].
7. A compound according to claim 2, wherein Q is [Q-2].
8. A compound according to claim 2, wherein Q is [Q-3].
9. A compound according to claim 2, wherein Q is [Q-4].
10. A compound according to claim 3, wherein Q is [Q-1].
1 1. A compound according to claim 3, wherein Q is [Q-2].
12. A compound according to claim 3, wherein Q is [Q-3].
13. A compound according to claim 3, wherein Q is [Q-4].
14. A compound according to claim 3, wherein Q is [Q-1]; and R2 is trifluoromethyl.
15. A compound according to claim 3, wherein Q is [Q-2]; and R2 is trifluoromethyl.
16. A compound according to claim 3, wherein Q is [Q-3]; and R2 is trifluoromethyl.
17. A compound according to claim 3, wherein Q is [Q-4]; and R2 is trifluoromethyl.
18. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoromethyl; and B is -OR10.
19. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoromethyl; and B is -NHR10.
20. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoromethyl; B is -OR10; and R10 is C3-C6 alkynyl.
21. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoro methyl; B is -OR10; and R10 is (C 1-C6 alkoxy)carbonyl C1-C6 alkyl.
22. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoromethyl; B is -OR10; and R10 is 1-(C1-C6 alkoxy)carbonylethyl.
23. A compound according to claim 3, wherein Q is [Q-1]; R2 is trifluoromethyl; B is -OR10; and R10 is (C1-C6 alkoxy)carbonylmethyl.
24. A compound according to claim 3, wherein Q is [Q-2]; R2 is trifluoromethyl; Z1 is oxygen; n is 1; R4 is hydrogen; and R5 is C3-C6 alkynyl.
25. A compound according to claim 2, wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-1]; X is fluorine; Y is chlorine; and B is propargyloxy.
26. A compound according to claim 2, wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-1]; X is fluorine; Y is chlorine; and B is
1-(ethoxycarbonyl)ethoxy.
27. A compound according to claim 2, wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-1]; X is fluorine; Y is chlorine; and B is
1-(methoxycarbonyl)ethoxy.
28. A compound according to claim 2, wherein R1 is hydrogen; R2 is trifluoromethyl; R3 is methyl; Q is [Q-2]; X is fluorine; Z1 is oxygen; n is 1 ; R4 is hydrogen; and R5 is propargyl.
29. A process for producing a compound according to claim 1 , which comprises reacting a compound of the formula:
wherein R1 is hydrogen or C1 -C3 alkyl; R2 is C1-C6 alkyl optionally substituted with one or more halogen atoms; and Q is substituted phenyl, with a compound of the ffrmula: R3-D [3] wherein R3 is C1-C6 alkyl optionally substituted with one or more halogen atoms, C3-C6 alkenyl, or C3-C6 alkynyl; and D is chlorine, bromine, iodine, methanesulfonyloxy, trifluoromethanesulfonyloxy, or p-toluenesulfonyloxy.
30. A herbicidal composition comprising, as an active ingredient, a herbicidally effective amount of the compound according to claim 1, and an inert carrier or diluent.
31. A method for controlling unfavorable weeds, which comprises applying a herbicidally effective amount of the compound according to claim 1 to an area where the unfavorable weeds grow or will grow.
32. Use of the compound according to claim 1 as a herbicide.
33. A compound of the formula:
wherein R1 is hydrogen or C1-C3 alkyl; R21 is C1-C3 alkyl substituted with one or more halogen atoms; and Q is substituted phenyl.
34. A compound according to claim 33, wherein Q is [Q-1], [Q-2], [Q-3], [Q-4], or [Q-5] as defined in claim 2.
35. A compound according to claim 33 or 34, wherein R21 is trifluoromethyl.
36. A compound according to claim 34, wherein Q is [Q-1].
37. A process for producing a compound of the formula:
wherein Q is substituted phenyl; R 1 is hydrogen or C1-C3 alkyl; and R2 is C 1-C3 alkyl optionally substituted with one or more halogen atoms, which comprises reacting a compound of the formula: wherein Q and R1 are as defined above; and R19 and R20 are independently C1-C3 alkyl, with a compound of the formula:
wherein R2 is as defined above.
38. A compound according to claim 2, wherein Q is [Q-1] and R2 is C1-C3 alkyl substituted with one or more halogen atoms.
EP96925969A 1995-08-10 1996-08-01 Pyrimidin-4-one derivatives, their use as herbicides, intermediates for their production and processes for producing these compounds Withdrawn EP0850229A1 (en)

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US4725600A (en) * 1984-07-13 1988-02-16 Fujisawa Pharmaceutical Co., Ltd. Pyrimidine compounds having activity as a cardiotonic anti-hypertensive cerebrovascular vasodilator and anti-platelet aggregation agent
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DE3816994A1 (en) * 1988-05-19 1989-11-30 Hoechst Ag Herbicides based on 4-hydroxypyrimidine derivatives
EP0544166A3 (en) * 1991-11-26 1993-11-03 Hoffmann La Roche Cephalosporinderivatives
JPH05262765A (en) * 1992-03-18 1993-10-12 Sumitomo Chem Co Ltd Benzofuran derivative and herbicide containing the same as active ingredient
BR9301666A (en) * 1992-04-28 1993-11-03 Sumitomo Chemical Co COMPOUND, INTERMEDIATE COMPOUND, HERBICIDE COMPOSITION, PROCESS FOR EXTERMINING UNWANTED WEEDS, USE OF THIS COMPOUND AND PROCESS TO PRODUCE IT
US5726124A (en) * 1992-07-17 1998-03-10 Rohm And Haas Company 2-arylpyrimidines and herbicidal use thereof
US5476834A (en) * 1993-03-17 1995-12-19 Sumitomo Chemical Company, Limited Dihydrobenzofuran derivatives, their production and use
US5750549A (en) * 1996-10-15 1998-05-12 Merck & Co., Inc. Cycloalkyl tachykinin receptor antagonists

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9706150A1 *

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